Reidar Lund

• Urreizti, Eric Gómez; Molina, Paula Malo de; Pagnacco, Carlo Andrea; Pomposo, Jose A.; Lund, Reidar & Barroso-Bujans, Fabienne (2026). Ultrasmall Nanogels from Intramolecular Cross-Linking of (Hyper)Branched Cyclic Polyglycerols with Diboronic Acids. Macromolecules. ISSN 0024-9297. 59(7), p. 3975–3988. doi: 10.1021/acs.macromol.5c02780. Full text in Research Archive
• Cezar, Henrique Musseli; Berton, Giacomo; Lorenzetto, Tommaso; Zorzi, Sandro; Foumthuim, Cedrix J. Dongmo & Szostak, Szymon Mikolaj [Show all 15 contributors for this article] (2026). Self-Assembly of Unconventional Triphenylene-Based Frustrated Amphiphile in Solution. Langmuir. ISSN 0743-7463. 42(6), p. 4507–4517. doi: 10.1021/acs.langmuir.5c05203. Full text in Research Archive Show summary

  Unconventional amphiphilic molecules having a rigid hydrophobic central unit and flexible or semiflexible hydrophilic chains on the rim have proven valuable in several technological applications, for example, host–guest chemistry. The further presence of alternating hydrophobic and hydrophilic tails complicates the definition of clear core and shell regions, resulting in complex segregation and frustrated self-assembly. In this study, we investigate symmetric triphenylene-based amphiphilic derivatives with alternating benzyl and alkylsulfonate groups. We characterize their self-assembly in water and different solutions using several experimental techniques, including NMR, atomic force microscopy, dynamic light scattering, and small-angle X-ray and neutron scattering, alongside extensive molecular dynamics simulations, including both atomistic and coarse-grained integrative modeling with metainference. In aqueous solutions, these amphiphiles form stacked assemblies, adopting alternate up–down conformations driven by π-stacking of up to six molecules. The introduction of NaCl salt screens unfavorable electrostatic interactions, thus promoting further π-stacking and leading to the formation of larger elongated aggregates.

• Sørensen, Henrik Vinther; Canals, Mateu Montserrat; Coder, Ayla Steffensen; Prévost, Sylvain; Krueger, Susan & Vaaje-Kolstad, Gustav [Show all 9 contributors for this article] (2026). Tangled Up in Fibers: How a Multidomain Lytic Polysaccharide Monooxygenase Binds Its Chitin Substrate. ACS Applied Materials & Interfaces. ISSN 1944-8244. doi: 10.1021/acsami.5c24418. Full text in Research Archive Show summary

  Lytic polysaccharide monooxygenases (LPMOs) are redox enzymes that bind to and oxidize insoluble carbohydrate substrates such as chitin or cellulose. This class of enzymes has attracted considerable attention due to their ability to convert biomaterials of high abundance into oligosaccharides that can be useful for producing biofuels and bioplastics. However, processes at the interface between solution and insoluble substrates represent a major challenge to biochemical and structural characterization. Here, we investigated the four-domain LPMO from Vibrio cholerae, N-acetyl glucosamine binding protein A (GbpA), to elucidate how it docks onto its insoluble substrate with its two terminal domains. First, we developed a protocol that allowed GbpA and chitin to form a stable complex in suspension, overcoming incompatibilities of the two binding partners with respect to pH. After determining the small-angle neutron scattering (SANS) contrast match point for chitin (47% D2O), we characterized the mesoscale structure of GbpA in complex with chitin by SANS and complemented the results with negative-stain electron microscopy. We found that GbpA binds rapidly to chitin, where it coats the chitin fibers and smooths their surface. In some locations, GbpA binding induces the formation of protein–chitin clumps containing a large number of GbpA molecules. Together, this suggests how the secretion of GbpA efficiently prepares the ground for microcolony formation by the bacteria.

• Lund, Reidar; Willner, Lutz & Holderer, Olaf (2025). Structure and Chain Dynamics of Self-Healing Telechelic Polymer Networks. Macromolecules. ISSN 0024-9297. 58(18), p. 9754–9762. doi: 10.1021/acs.macromol.5c01216. Full text in Research Archive Show summary

  The development of self-healing materials, which are capable of reforming into their original structure following rupture and damage, represents a fascinating and important area of research, with a wide range of potential applications. Telechelic polymers, defined as polymers with functional chain ends such as hydrophobically end-modified polymers, serve as prime examples of systems capable of forming hydrogel networks with transient bonding structures. In this study, we investigate the internal chain dynamics and self-diffusion of hydrogel networks made from telechelic polymers, employing selective contrast variation for small-angle neutron scattering and neutron spin echo spectroscopy. We show that the chain dynamics in the gel follow regular Zimm dynamics without any apparent evidence of restricted motion due to chain connectivity, possibly because the lifetime of the bonds is short. On the other hand, the micellar cores show slow relaxation, reflecting the restricted motion due to the connectivity and crowdedness of the system. The study highlights the decoupling between the slow dynamics of the micellar cores, which play a critical role in the rheological response, and the fast, relatively unconstrained chain dynamics that contribute to their “self-healing” properties. The results provide detailed insight into the multiscale dynamics in hydrogels with transient bonds useful for applications of these types of materials, natural or synthetic.

• Gupta, Kushol; Sekulic, Nikolina; Allu, Praveen Kumar; Sapp, Nicklas; Huang, Qingqiu & Sarachan, Kathryn [Show all 13 contributors for this article] (2025). Solution conformational differences between conventional and CENP-A nucleosomes are accentuated by reversible deformation under high pressure. Chromosome Research. ISSN 0967-3849. 33(1). doi: 10.1007/s10577-025-09769-z. Full text in Research Archive Show summary

  Abstract Solution-based interrogation of the physical nature of nucleosomes has its roots in X-ray and neutron scattering experiments, including those that provided the initial observation that DNA wraps around core histones. In this study, we performed a comprehensive small-angle scattering study to compare canonical nucleosomes with variant centromeric nucleosomes harboring the histone variant, CENP-A. We used nucleosome core particles (NCPs) assembled on an artificial positioning sequence (Widom 601) and compared these to those assembled on a natural α-satellite DNA from human centromeres. We establish the native solution properties of octameric H3 and CENP-A NCPs using analytical ultracentrifugation (AUC), small-angle X-ray scattering (SAXS), and contrast variation small-angle neutron scattering (CV-SANS). Using high-pressure SAXS (HP-SAXS), we discovered that both histone and DNA sequence have an impact on the stability of octameric nucleosomes in solution under high pressure (300 MPa), with evidence of reversible unwrapping in these experimental conditions. Both canonical nucleosomes harboring conventional histone H3 and their centromeric counterparts harboring CENP-A have a substantial increase in their radius of gyration, but this increase is much less prominent for centromeric nucleosomes. More broadly for chromosome-related research, we note that as HP-SAXS methodologies expand in their utility, we anticipate this will provide a powerful solution-based approach to study nucleosomes and higher-order chromatin complexes.

• Vogelaar, Thomas Daniel; Schwärzer, Kuno; Pedersen, Jan Skov & Lund, Reidar (2025). Antibiotic vesicles based on peptide-polymer complex coacervation. Journal of Colloid and Interface Science. ISSN 0021-9797. doi: 10.1016/j.jcis.2025.139409. Full text in Research Archive Show summary

  Antimicrobial peptides (AMPs) represent a promising strategy for developing new antibiotic formulations to combat multidrug-resistant bacterial infections. However, the therapeutic application of colistin, a potent AMP, is largely limited to last-resort scenarios due to its associated cytotoxicity and low stability in solution. In our investigation of complex coacervation techniques for creating effective drug delivery platforms, we discovered the formation of complex coacervate core vesicles (C3Vs) upon mixing cationic colistin with partially oppositely charged poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) diblock copolymers. This approach opens new avenues for enhancing the therapeutic potential of colistin while mitigating its drawbacks. To gain deeper insights into these structures, we prepared C3Vs using both protonated and partially deuterated PEO-b-PMAA in combination with colistin. Through the development of a tailored analytical vesicle scattering model, we describe our small-angle X-ray and neutron scattering (SAXS/SANS) data and quantify the structure and composition of C3Vs for the first time in great detail. We report net-neutral vesicles with diameters of 100-190 nm with a fixed vesicle wall dimension that has a total nominal thickness of ≈ 17-18 nm. Notably, while the wall thickness remains invariant, the inner radius of the vesicle (water core) varies significantly with experimental conditions, such as concentration, charge fraction, incubation time, and ionic strength. Increasing the ionic strength to physiological levels, we find smaller assembled structures that resemble micelles rather than vesicles. Interestingly, time-resolved SANS experiments show that the vesicles in salt-free solution are exceptionally stable with no detectable exchange kinetics between vesicles within 24 hours. We expect the structural elucidation of these systems in multiple conditions to provide valuable insights for future research, particularly in developing vesicular drug delivery systems.

• Koynarev, Vladimir Rosenov; Nader, Manuela Leal; Borgos, Kari Kristine Almåsvold; Cezar, Henrique Musseli; Narayanan, Theyencheri & Porcar, Lionel [Show all 8 contributors for this article] (2025). Structural pores not required: Antimicrobial peptides induce ion permeabilization of lipid membranes through transient water channels. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 122(44). doi: 10.1073/pnas.2517944122. Full text in Research Archive Show summary

  Antimicrobial peptides (AMPs) are highly potent and broad-spectrum antibiotics, found as components of the innate immune system in almost all forms of life. Despite being commonly accepted that the mechanism of action of AMPs is associated with the permeabilization of the cell membrane, the structural and dynamical means by which this occurs are still heavily debated. In this work, we employ experimental time-resolved small angle X-ray scattering to follow in real time the AMP-induced ion transport in lipid vesicles, while simultaneously resolving the membrane structure and peptide partitioning. For several natural AMPs, we show that they can effectively permeabilize the lipid membrane despite only binding peripherally to the outer membrane leaflet. Our experiments reveal rapid ion transport associated with AMP binding, yielding salt equilibration in a few tens of milliseconds, while not detecting evidence of transversal and structurally stable peptide pores. On the contrary, new analysis of previously reported all-atom molecular dynamics simulations shows that lipid flip-flop, accelerated by the peripherally bound peptides, leads to the formation of transient, ion-conducting water channels. A corresponding diffusional model indicates that such short-lived, transient pores explain the observed ion transport better than stable pores.

• Muthukamatchi, Anu; Alcock, Benjamin & Lund, Reidar (2025). Influence of Fluorine Content and Carbon Black Loadings on Fluoroelastomers for CO2 Pipeline Transport. ACS Applied Polymer Materials. 7(17), p. 11827–11840. doi: 10.1021/acsapm.5c02277. Full text in Research Archive Show summary

  Fluoroelastomers (FKMs) are widely used in oilfield seals due to their chemical resistance and thermal stability, yet their performance under liquid carbon dioxide (LCO2) conditions remains insufficiently understood. This study investigates the performance of two FKMs, a copolymer (FKM1) and a terpolymer (FKM2), each formulated with carbon black (CB) loadings of 0, 25, and 37.5 wt %, under exposure to liquid CO2 at 23 ± 2 °C and 58 ± 2 bar, which are representative of typical CO2 pipeline transport conditions. The compounds were characterized through in-situ swelling measurements and, before and after exposure, using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), tensile testing, and compression set (CS). Morphological evaluation was conducted using scanning electron microscopy (SEM) on cryogenically fractured samples. The results show that FKM2, which contains higher fluorine content and estimated cross-linking density, exhibits lower swelling during and after decompression, improved dimensional recovery, and more stable mechanical performance following CO2 exposure compared to FKM1. The addition of CB reduces CO2-induced rapid gas decompression (RGD) effects and increases tensile strength and stiffness, while reducing elastic recovery at higher filler loadings. Wide-angle X-ray scattering (WAXS) shows negligible changes in polymer structure following exposure to LCO2 in both FKM types. Overall, this study highlights that factors such as cross-link density, fluorine content, and carbon black loading are important when selecting fluorinated elastomers for CO2 transport applications.

• Lauretis, Angela de; Agger, Anne Eriksson; Pal, Antara; Pedersen, Jan Skov; Szostak, Szymon Mikolaj & Lund, Reidar [Show all 10 contributors for this article] (2025). Balancing sterilization and functional properties in Poloxamer 407 hydrogels: comparing heat and radiation techniques. Regenerative Biomaterials. 12. doi: 10.1093/rb/rbaf005. Full text in Research Archive Show summary

  Poloxamer 407, also known as Pluronic® F127, is gaining interest in the cosmetic, biomedical, and pharmaceutical fields for its biocompatibility, safety, and thermosensitive properties. Ensuring sterility is critical in clinical applications, and sterilization is often preferred over aseptic processing. However, sterilization can impact the hydrogel's functional properties. In this study, we investigate the effects of steam heat (121°C, 20 min), dry heat (160°C, 1 h), gamma irradiation (25 kGy), and electron beam (e-beam) irradiation (15 kGy and 25 kGy) on a 30%w/v Poloxamer 407 hydrogel formulation. Our analysis encompasses gelling properties, pH, Fourier-transform infrared (FTIR) spectroscopy, Gel Permeation Chromatography (GPC), Small-angle X-ray scattering (SAXS), rheology, swelling, degradation by-products, and lactate dehydrogenase (LDH) release of the sterilised hydrogels, comparing them to a non-sterile counterpart. We demonstrated that heat sterilisation alters the hydrogel’s gelling and structural properties due to water evaporation and oxidation under harsh temperature conditions, especially when applying the dry heat method. Gamma irradiation proved unsuitable, resulting in an acidic and cytotoxic hydrogel due to oxidative degradation. In contrast, e-beam irradiation preserves the hydrogel's elasticity, gelling, and structural properties while enhancing mechanical resilience and moderating swelling. Therefore, e-beam irradiation within the 15 – 25 kGy range appears to be the most suitable method for sterilizing a 30%w/v Poloxamer 407 hydrogel.

• Cárdenas, Marité; Bjørnestad, Victoria Ariel; Borgos, Kari Kristine Almåsvold & Lund, Reidar (2025). The integrity of the lipid bilayer structure is retained in natural occurring deep eutectic solvent water mixtures - a small angle X-ray scattering study. Physical Chemistry, Chemical Physics - PCCP. ISSN 1463-9076. 27(10248), p. 10258–10258. doi: 10.1039/d5cp00331h. Full text in Research Archive Show summary

  Natural occurring deep eutectic solvents (NADES) are solvents made of metabolites occurring in living organisms, and are thought to play a special role in plants especially given that some of these metabolites exist in concentrations as high as 1 M. NADES have properties similar to ionic liquids, and have been shown to protect enzymes against loss of activity as well as proteins against thermal denaturation. Here, we explore the structure of lipid vesicles in NADES rich aqueous solutions and compare to concentrated saline aqueous solutions matching the various NADES osmolarity. The vesicle structure was analysed by small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Two types of NADES were prepared using choline chloride and glucose or maleic acid at a molar ratio of 1 : 1 giving the solvents a neutral or an acidic nature, respectively. The stability of the vesicles in the various solvents was measured against time and temperature. The results of this work demonstrate that lipid bilayers retain their structure in NADES rich aqueous solutions as compared to pure water, in contrast to high saline aqueous solutions. Moreover, the vesicles are more stable against sedimentation and aggregation in NADES than in water.

• Muthukamatchi, Anu; Lund, Reidar; Alcock, Benjamin & Ansaloni, Luca (2025). The Effect of Crosslinking Density and Carbon Black Content on the Performance of EPDM for CO2 Transport Applications. Journal of Applied Polymer Science. ISSN 0021-8995. 142(32). doi: 10.1002/app.57289. Full text in Research Archive Show summary

  The escalating demand for efficient and sustainable carbon capture and storage technologies requires robust materials capable of withstanding the challenging temperature and pressure conditions encountered in CO2 transport systems. To address this need, this research investigates the suitability of ethylene propylene diene monomer (EPDM) elastomers as potential materials for carbon dioxide (CO2) transport systems, such as seals and gaskets. This research presents a detailed characterization of the effect of varying degrees of crosslink density and carbon black content. Insights into CO2 uptake and reduction in glass transition temperature (Tg) following exposure to liquid carbon dioxide (LCO2) are presented. The work also focuses on the investigation of CO2 permeability, diffusivity, and solubility in EPDM using a constant volume and variable pressure method at different temperature and pressure conditions. The work extends to the extraction of EPDM using various solvents that are liquid at ambient conditions, examining their subsequent changes in thermal, mechanical, and CO2 transport properties.

• Szostak, Szymon Mikolaj; König, Nico; Willner, Lutz & Lund, Reidar (2025). Modulating melting points in micellar cores: influence of the corona chain length on the core confinement in binary mixed block copolymer micelles. Soft Matter. ISSN 1744-683X. 21(10), p. 1895–1906. doi: 10.1039/d4sm01303d. Full text in Research Archive Show summary

  Self-assembly of polymers with crystallizable blocks may lead to micelles with ordered, gel-like or crystalline cores. Here we investigate binary mixtures of n-alkyl-poly(ethylene oxide), Cn-PEOx (n = 28, x = 3–20 kDa) and study their self-assembly to gain insight into the effect of confinement on the core-crystallization and micellar structure. By employing identical core block length but varying corona block lengths, the size of the core can be tuned by variation of the block ratios. The micelles were characterized by small-angle X-ray scattering (SAXS) to gain insight into the overall and internal structure, including aggregation number, core size, and density distribution of the corona. SAXS curves from examined samples showed a characteristic pattern of spherical core–shell micelles but with broader corona distribution in the binary mixtures as compared to the neat samples. The structural parameters of the micelles were extracted from the SAXS data by employing a spherical core–shell model with dual density profiles in the core. We found that the aggregation number decreases as PEO length increases following a power law predicted in the literature. Furthermore, the melting point and melting enthalpy of crystalline alkyl cores were closely inspected by densitometry and differential scanning calorimetry (DSC). Correlating the core radius obtained from SAXS, we found that the melting point depression caused by the self-confinement in the micellar core can be described by the Gibbs–Thomson equation. These results show that the micellar structure and phase transition of the semicrystalline core can be easily tuned through blending diblock copolymers with different corona block lengths.

• Vogelaar, Thomas Daniel; Torjusen, Henrik; Narayanan, Theyencheri & Lund, Reidar (2025). The Kinetic Pathways for the Formation of Complex Coacervate Micelles of Antimicrobial Peptides and Block Copolymers. Macromolecules. ISSN 0024-9297. 58(1), p. 158–168. doi: 10.1021/acs.macromol.4c02077. Full text in Research Archive Show summary

  The conceptual application of complex coacervate core micelles (C3Ms) as drug delivery vehicles has obtained significant interest over the past several decades. Although C3Ms show promise in targeting specific body areas and improving drug circulation times, their low reproducibility and limited stability have hindered their progression to clinical trials and commercial viability. One of the major obstacles is the lack of understanding of the formation and growth kinetics of C3Ms. Since their structure is often controlled kinetically rather than thermodynamically, this insight is essential for achieving good reproducibility and stability of C3M drug delivery vehicles. Time-resolved small-angle X-ray scattering (TR-SAXS) offers excellent insights by resolving spatiotemporal kinetic processes on nanometer/millisecond scales. Here, we investigate the formation kinetics of C3Ms comprised of the antimicrobial peptide, colistin, and poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA). Using TR-SAXS coupled to stopped-flow mixing, we have identified three distinct steps in the mechanism of this complex coacervation system: nucleation, fusion, and single chain/ion-pair insertion. Nucleation cannot be experimentally resolved as it is completed during the mixing process. The fusion kinetics proceed as a first-order reaction with relaxation times of approximately 50–85 ms. The driving force for fusion is larger at increased concentrations. Chain/pair insertion occurs at relaxation times of 15–25 s, where larger remaining size mismatches (higher dispersity) drive the final equilibration process. As expected, the structural formation is concentration-dependent, providing a handle to acquire control over the size and dispersity of these kinetically trapped C3Ms. These findings contribute to a deeper understanding of C3M formation and stability, potentially advancing the development of C3M-based drug delivery systems.

• Koynarev, Vladimir Rosenov; Vogelaar, Thomas Daniel; Moqadam, Mahmoud; Reuter, Nathalie & Lund, Reidar (2025). Colistin does not self-assemble at physiologically relevant conditions. Colloid and Interface Science Communications. 65. doi: 10.1016/j.colcom.2025.100824. Full text in Research Archive Show summary

  Antimicrobial peptides (AMPs) have shown great potential against the ongoing rise of multi-drug resistant bacteria because of their high potency and effectiveness. Their clinical utility has, however, remained limited due to their severe side effects. As an exception, colistin (polymyxin E) is currently utilized as a last-resort option against severe gram-negative infections despite being cyto- and nephrotoxic. The ongoing efforts to reduce these side effects are hampered by the generally poor understanding of its mode of action and behavior in solution. A key question that has been debated is whether colistin self-assembles into micelles or remains as unimers in solution. Herein, we used synchrotron small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), and molecular dynamics (MD) to show that colistin does not self-assemble in a wide range of physiologically relevant conditions. These contrasting findings, compared to previously reported results, provide important new insights into the behavior of colistin, aiding the understanding and potential improvement of this relevant AMP-based antibiotic.

• Pagnacco, Carlo Andrea; Alvarez-Fernandez, Alberto; Maestro, Armando; Román, Estíbaliz González de San; Lund, Reidar & Barroso-Bujans, Fabienne (2024). Varying the Core Topology in All-Glycidol Hyperbranched Polyglycerols: Synthesis and Physical Characterization. Macromolecular rapid communications. ISSN 1022-1336. doi: 10.1002/marc.202400791. Full text in Research Archive Show summary

  In the present study, low molecular weight cyclic polyglycidol is used as a macroinitiator for hypergrafting glycidol and producing cyclic graft hyperbranched polyglycerol (cPG-g-hbPG) in the molecular weight range of 103–106 g mol−1. Linear graft hyperbranched polyglycerol (linPG-g-hbPG) and hyperbranched polyglycerol (hbPG) are prepared as reference samples. This creates a family of hbPG structures with cyclic, linear, and star cores, allowing to evaluate their properties in solution and in bulk. The morphology study of the high molecular weight structures using atomic force microscopy revealed a spherical shape for cPG-g-hbPG and hbPG, and a cylindrical shape for linPG-g-hbPG in the nanometric range. Small angle X-ray scattering confirmed the compact particle-like structure of this family of hbPG architectures. Interestingly, the glass transition temperature showed a structure dependence, with cPG-g-hbPG having the highest values and hbPG having the lowest values for the same molecular weight. This study is a step forward in the generation of water-soluble polymers with tailored structure and functionality for advanced applications.

• Cezar, Henrique Musseli; Bjørnestad, Victoria Ariel; Prévost, Sylvain François; Lund, Reidar & Cascella, Michele (2024). Beyond Core–Shell Micellar Structures: Complex Structures in Simple Surfactants. Small Structures. doi: 10.1002/sstr.202400553. Full text in Research Archive Show summary

  Small-angle X-ray/neutron scattering (SAXS/SANS) techniques provide valuable nanostructural information of self-assembling molecules. However, extracting the information from these experiments can be a challenging task, usually relying on predetermined assumptions. Conventional models for surfactant micelles consider a core–shell structure with a hydrophobic tail encapsulated by the hydrophilic part. This approach is successful in many cases but can fail even for common surfactants such as Triton X-100 (TX-100). SAXS and SANS combined with Metainference molecular simulations are employed to investigate TX-100 assemblies, showing how more complex models, with diffuse core–shell boundaries, multilayering, and polydispersity, are needed to explain the aggregation. This is the first time that Metainference is employed with SAXS and SANS simultaneously to obtain the structural ensemble of assemblies. Compared to regular micelles formed by chemically similar C12EO10 molecules, the role of the hydrophobic core in micellization is discussed, finding that the relatively shorter and less hydrophobic tail of TX-100 favors polymorphism.

• Koynarev, Vladimir Rosenov; Borgos, Kari Kristine Almåsvold; Kohlbrecher, Joachim; Porcar, Lionel; Nielsen, Josefine Eilsø & Lund, Reidar (2024). Antimicrobial Peptides Increase Line Tension in Raft-Forming Lipid Membranes. Journal of the American Chemical Society. ISSN 0002-7863. 146(30), p. 20891–20903. doi: 10.1021/jacs.4c05377. Full text in Research Archive Show summary

  The formation of phase separated membrane domains is believed to be essential for the function of the cell. The precise composition and physical properties of lipid bilayer domains play crucial roles in regulating protein activity and governing cellular processes. Perturbation of the domain structure in human cells can be related to neurodegenerative diseases and cancer. Lipid rafts are also believed to be essential in bacteria, potentially serving as targets for antibiotics. An important question is how the membrane domain structure is affected by bioactive and therapeutic molecules, such as surface-active peptides, which target cellular membranes. Here we focus on antimicrobial peptides (AMPs), crucial components of the innate immune system, to gain insights into their interaction with model lipid membranes containing domains. Using small-angle neutron/X-ray scattering (SANS/SAXS), we show that the addition of several natural AMPs (indolicidin, LL-37, magainin II, and aurein 2.2) causes substantial growth and restructuring of the domains, which corresponds to increased line tension. Contrast variation SANS and SAXS results demonstrate that the peptide inserts evenly in both phases, and the increased line tension can be related to preferential and concentration dependent thinning of the unsaturated membrane phase. We speculate that the lateral restructuring caused by the AMPs may have important consequences in affecting physiological functions of real cells. This work thus shines important light onto the complex interactions and lateral (re)organization in lipid membranes, which is relevant for a molecular understanding of diseases and the action of antibiotics.

• Vogelaar, Thomas Daniel; Szostak, Szymon Mikolaj & Lund, Reidar (2024). Coacervation in Slow Motion: Kinetics of Complex Micelle Formation Induced by the Hydrolysis of an Antibiotic Prodrug. Molecular Pharmaceutics. ISSN 1543-8384. doi: 10.1021/acs.molpharmaceut.4c00579. Full text in Research Archive Show summary

  Colistin methanesulfonate (CMS) is the less-toxic prodrug of highly nephrotoxic colistin. To develop and understand highly necessary new antibiotic formulations, the hydrolysis of CMS to colistin must be better understood. Herein, with the addition of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) to CMS, we show that we can follow the hydrolysis kinetics, employing small-angle X-ray scattering (SAXS) through complex coacervation. During this hydrolysis, hydroxy methanesulfonate (HMS) groups from CMS are cleaved, while the newly formed cationic amino groups complex with the anionic charge from the PMAA block. As the hydrolysis of HMS groups is slow, we can follow the complex coacervation process by the gradual formation of complex micelles containing activated antibiotics. Combining mass spectrometry (MS) with SAXS, we quantify the hydrolysis as a function of pH. Upon modeling the kinetic pathways, we found that complexation only happens after complete hydrolysis into colistin and that the process is accelerated under acidic conditions. At pH = 5.0, effective charge switching was identified as the slowest step in the CMS conversion, constituting the rate-limiting step in colistin formation.

• Pagnacco, Carlo Andrea; Kravicz, Marcelo H.; Sica, Francesco Saverio; Fontanini, Veronica; Román, Estibaliz González de San & Lund, Reidar [Show all 8 contributors for this article] (2024). In Vitro Biocompatibility and Endothelial Permeability of Branched Polyglycidols Generated by Ring-Opening Polymerization of Glycidol with B(C<inf>6</inf>F<inf>5</inf>)<inf>3</inf> under Dry and Wet Conditions. Biomacromolecules. ISSN 1525-7797. doi: 10.1021/acs.biomac.4c00210. Full text in Research Archive Show summary

  Polyglycidol or polyglycerol (PG), a polyether widely used in biomedical applications, has not been extensively studied in its branched cyclic form (bcPG), despite extensive research on hyperbranched PG (HPG). This study explores the biomedical promise of bcPG, particularly its ability to cross the blood–brain barrier (BBB). We evaluate in vitro biocompatibility, endothelial permeability, and formation of branched linear PG (blPG) as topological impurities in the presence of water. Small angle X-ray scattering in solution revealed a fractal dimension of approximately two for bcPG and the mixture bc+blPG, suggesting random branching. Comparisons of cytotoxicity and endothelial permeability between bcPG, bc+blPG, and HPG in a BBB model using hCMEC/D3 cells showed different biocompatibility profiles and higher endothelial permeability for HPG. bcPG showed a tendency to accumulate around cell nuclei, in contrast to the behavior of HPG. This study contributes to the understanding of the influence of polymer topology on biological behavior.

• Vogelaar, Thomas Daniel; Torjusen, Henrik & Lund, Reidar (2024). Size-controlled antimicrobial peptide drug delivery vehicles through complex coacervation. Soft Matter. ISSN 1744-683X. doi: 10.1039/d4sm01157k. Full text in Research Archive Show summary

  Due to the escalating threat of the pathogens’ capability of quick adaptation to antibiotics, finding new alternatives is crucial. Although antimicrobial peptides (AMPs) are highly potent and effective, their therapeutic use is limited‚ as they are prone to enzymatic degradation, are cytotoxic and have low retention. To overcome these challenges, we investigate the complexation of the cationic AMP colistin with diblock copolymers poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) forming colistin–complex coacervate core micelles (colistin–C3Ms). We present long-term stable kinetically controlled colistin–C3Ms that can be prepared from several block lengths of PEO-b-PMAA polymers, where the polymerisation degree governs the overall micellar size. To achieve precise control over size and polydispersity, which are crucial for drug delivery applications, we investigate the hybridisation of PEO-b-PMAA polymers with varying chain lengths or PMAA homopolymers in ternary complex coacervation systems with colistin. This results in size-tunable colistin–C3Ms, ranging, depending on the mixing ratios, from micellar sizes of 26 nm to 100 nm. With size tunability at rather narrow size distributions and high stability, ternary colistin–C3Ms offer potential advancements in C3M drug delivery, paving the way for more effective and targeted treatments for bacterial infections in precision medicine.

• Vogelaar, Thomas Daniel; Agger, Anne Eriksson; Reseland, Janne Elin; Linke, Dirk; Jenssen, Håvard & Lund, Reidar (2024). Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers. Biomacromolecules. ISSN 1525-7797. 25(7), p. 4267–4280. doi: 10.1021/acs.biomac.4c00337. Full text in Research Archive Show summary

  To combat the ever-growing increase of multidrug-resistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

• Bjørnestad, Victoria Ariel; Li, Xinmeng; Tribet, Christophe; Lund, Reidar & Cascella, Michele (2023). Micelle kinetics of photoswitchable surfactants: Self-assembly pathways and relaxation mechanisms. Journal of Colloid and Interface Science. ISSN 0021-9797. 646, p. 883–899. doi: 10.1016/j.jcis.2023.05.057. Full text in Research Archive Show summary

  Hypothesis: A key question in the kinetics of surfactant self-assembly is whether exchange of unimers or fusion/fission of entire micelles is the dominant pathway. In this study, an isomerizable surfactant is used to explore fundamental out-of-equilibrium kinetics and mechanisms for growth and dissolution of micelles. Experiments: The kinetics of cationic surfactant 4-butyl-4'-(3-trimethylammoniumpropoxy)-phenylazobenzene was studied using molecular dynamics simulations. The fusion and exchange processes were investigated using umbrella sampling. Equilibrium states were validated by comparison with small-angle X-ray scattering data. The photo-isomerization event was simulated by modifying the torsion potential of the photo-responsive group to emulate the trans-to-cis transition. Findings: Micelle growth is dominated by unimer exchange processes, whereas, depending on the conditions, dissolution can occur both through fission and unimer expulsion. Fusion barriers increase steeply with the aggregation number making this an unlikely pathway to equilibrium for micelles of sizes that fit with the experimental data. The barriers for unimer expulsion remain constant and are much lower for unimer insertion, making exchange more likely at high aggregation. When simulating photo-conversion events, both fission and a large degree of unimer expulsion can occur depending on the extent of the out-of-equilibrium stress that is put on the system.

• Bjørnestad, Victoria Ariel & Lund, Reidar (2023). Pathways of Membrane Solubilization: A Structural Study of Model Lipid Vesicles Exposed to Classical Detergents. Langmuir. ISSN 0743-7463. 39(11), p. 3914–3933. doi: 10.1021/acs.langmuir.2c03207. Full text in Research Archive Show summary

  Understanding the pathways of solubilization of lipid membranes is of high importance for their use in biotechnology and industrial applications. Although lipid vesicle solubilization by classical detergents has been widely investigated, there are few systematic structural and kinetic studies where different detergents are compared under varying conditions. This study used small-angle X-ray scattering to determine the structures of lipid/detergent aggregates at different ratios and temperatures and studied the solubilization in time using the stopped-flow technique. Membranes composed of either of two zwitterionic lipids, DMPC or DPPC, and their interactions with three different detergents, sodium dodecyl sulfate (SDS), n-dodecyl-beta-maltoside (DDM), and Triton X-100 (TX-100), were tested. The detergent TX-100 can cause the formation of collapsed vesicles with a rippled bilayer structure that is highly resistant to TX-100 insertion at low temperatures, while at higher temperatures, it partitions and leads to the restructuring of vesicles. DDM also causes this restructuring into multilamellar structures at subsolubilizing concentrations. In contrast, partitioning of SDS does not alter the vesicle structure below the saturation limit. Solubilization is more efficient in the gel phase for TX-100 but only if the cohesive energy of the bilayer does not prevent sufficient partitioning of the detergent. DDM and SDS show less temperature dependence compared to TX-100. Kinetic measurements reveal that solubilization of DPPC largely occurs through a slow extraction of lipids, whereas DMPC solubilization is dominated by fast and burst-like solubilization of the vesicles. The final structures obtained seem to preferentially be discoidal micelles where the detergent can distribute in excess along the rim of the disc, although we do observe the formation of worm- and rodlike micelles in the case of solubilization of DDM. Our results are in line with the suggested theory that bilayer rigidity is the main factor influencing which aggregate is formed.

• Nielsen, Josefine Eilsø; Koynarev, Vladimir Rosenov & Lund, Reidar (2023). Peptide meets membrane: Investigating peptide-lipid interactions using small-angle scattering techniques. Current Opinion in Colloid & Interface Science. ISSN 1359-0294. 66. doi: 10.1016/j.cocis.2023.101709. Full text in Research Archive Show summary

  Peptide–lipid interactions play an important role in defining the mode of action of drugs and the molecular mechanism associated with many diseases. Model membranes consisting of simple lipid mixtures mimicking real cell membranes can provide insight into the structural and dynamic aspects associated with these interactions. Small-angle scattering techniques based on X-rays and neutrons (SAXS/SANS) allow in situ determination of peptide partition and structural changes in lipid bilayers in vesicles with relatively high resolution between 1-100 nm. With advanced instrumentation, time-resolved SANS/SAXS can be used to track equilibrium and nonequilibrium processes such as lipid transport and morphological transitions to time scales down to a millisecond. In this review, we provide an overview of recent advances in the understanding of complex peptide–lipid membrane interactions using SAXS/SANS methods and model lipid membrane unilamellar vesicles. Particular attention will be given to the data analysis, possible pitfalls, and how to extract quantitative information using these techniques.

• Carrer, Manuel; Nielsen, Josefine Eilsø; Cezar, Henrique Musseli; Lund, Reidar; Cascella, Michele & Silva, Thereza Amelia Soares da (2023). Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides. The Journal of Physical Chemistry Letters. 14(31), p. 7014–7019. doi: 10.1021/acs.jpclett.3c01284. Full text in Research Archive Show summary

  We report a physicochemical investigation of the lipid transport properties of model lipid membranes in the presence of the antimicrobial peptide indolicidin through comparisons of experimental SANS/SAXS scattering techniques to fully atomistic molecular dynamics simulations. In agreement with the experiment, we show that upon peripheral binding of the peptides, even at low concentrations, lipid flip-flop dynamics is greatly accelerated. Computer modeling elucidates the interplay between structural changes and lipid dynamics induced by peptides and proposes a mechanism for the mode of action of antimicrobial peptides, assessing the major role of entropy for the catalysis of the flipping events. The mechanism introduced here is universal for all peptides with preferential peripheral binding to the membrane as it does not depend on the specific amino acid sequence.

• Kim, Minsang; Cheon, Yeongmi; Shin, Dongmin; Choi, Jieun; Nielsen, Josefine Eilsø & Jeong, Myeong Seon [Show all 13 contributors for this article] (2023). Real-Time Monitoring of Multitarget Antimicrobial Mechanisms of Peptoids Using Label-Free Imaging with Optical Diffraction Tomography. Advanced Science. doi: 10.1002/advs.202302483. Full text in Research Archive Show summary

  Abstract Antimicrobial peptides (AMPs) are promising therapeutics in the fight against multidrug‐resistant bacteria. As a mimic of AMPs, peptoids with N ‐substituted glycine backbone have been utilized for antimicrobials with resistance against proteolytic degradation. Antimicrobial peptoids are known to kill bacteria by membrane disruption; however, the nonspecific aggregation of intracellular contents is also suggested as an important bactericidal mechanism. Here,structure‐activity relationship (SAR) of a library of indole side chain‐containing peptoids resulting in peptoid 29 as a hit compound is investigated. Then, quantitative morphological analyses of live bacteria treated with AMPs and peptoid 29 in a label‐free manner using optical diffraction tomography (ODT) are performed. It is unambiguously demonstrated that both membrane disruption and intracellular biomass flocculation are primary mechanisms of bacterial killing by monitoring real‐time morphological changes of bacteria. These multitarget mechanisms and rapid action can be a merit for the discovery of a resistance‐breaking novel antibiotic drug.

• Hatlem, Daniel; Christensen, Mikkel; Broeker, Nina; Kristiansen, Per Eugen; Lund, Reidar & Barbirz, Stefanie [Show all 7 contributors for this article] (2023). A trimeric coiled-coil motif binds bacterial lipopolysaccharides with picomolar affinity. Frontiers in Cellular and Infection Microbiology. 13. doi: 10.3389/fcimb.2023.1125482. Full text in Research Archive Show summary

  α-helical coiled-coils are ubiquitous protein structures in all living organisms. For decades, modified coiled-coils sequences have been used in biotechnology, vaccine development, and biochemical research to induce protein oligomerization, and form self-assembled protein scaffolds. A prominent model for the versatility of coiled-coil sequences is a peptide derived from the yeast transcription factor, GCN4. In this work, we show that its trimeric variant, GCN4-pII, binds bacterial lipopolysaccharides (LPS) from different bacterial species with picomolar affinity. LPS molecules are highly immunogenic, toxic glycolipids that comprise the outer leaflet of the outer membrane of Gram-negative bacteria. Using scattering techniques and electron microscopy, we show how GCN4-pII breaks down LPS micelles in solution. Our findings suggest that the GCN4-pII peptide and derivatives thereof could be used for novel LPS detection and removal solutions with high relevance to the production and quality control of biopharmaceuticals and other biomedical products, where even minuscule amounts of residual LPS can be lethal.

• Meuskens, Ina; Kristiansen, Per Eugen; Bardiaux, Benjamin; Koynarev, Vladimir Rosenov; Hatlem, Daniel & Prydz, Kristian [Show all 9 contributors for this article] (2023). A poly-proline II helix in YadA from Yersinia enterocolitica serotype O:9 facilitates heparin binding through electrostatic interactions. The FEBS Journal. ISSN 1742-464X. 291(4), p. 761–777. doi: 10.1111/febs.17001. Full text in Research Archive Show summary

  Poly‐proline II helices are secondary structure motifs frequently found in ligand‐binding sites. They exhibit increased flexibility and solvent exposure compared to the strongly hydrogen‐bonded α‐helices or β‐strands and can therefore easily be misinterpreted as completely unstructured regions with an extremely high rotational freedom. Here, we show that the adhesin YadA of Yersinia enterocolitica serotype O:9 contains a poly‐proline II helix interaction motif in the N‐terminal region. The motif is involved in the interaction of YadA O:9 with heparin, a host glycosaminoglycan. We show that the basic residues within the N‐terminal motif of YadA are required for electrostatic interactions with the sulfate groups of heparin. Biophysical methods including CD spectroscopy, solution‐state NMR and SAXS all independently support the presence of a poly‐proline helix allowing YadA O:9 binding to the rigid heparin. Lastly, we show that host cells deficient in sulfation of heparin and heparan sulfate are not targeted by YadA O:9 ‐mediated adhesion. We speculate that the YadA O:9 –heparin interaction plays an important and highly strain‐specific role in the pathogenicity of Yersinia enterocolitica serotype O:9.

• Bjørnestad, Victoria Ariel; Soto-Bustamante, Fernando; Tria, Giancarlo; Laurati, Marco & Lund, Reidar (2023). Beyond the standard model of solubilization: Non-ionic surfactants induce collapse of lipid vesicles into rippled bilamellar nanodiscs. Journal of Colloid and Interface Science. ISSN 0021-9797. 641, p. 553–567. doi: 10.1016/j.jcis.2023.03.037. Full text in Research Archive Show summary

  Hypothesis Although solubilization of lipid membranes has been studied extensively, questions remain regarding the structural pathways and metastable structures involved. This study investigated whether the non-ionic detergent Triton X-100 follows the classical solubilization pathway or if intermediate nanostructures are formed. Experiments Small angle X-ray and neutron scattering (SAXS/SANS) was used in combination with transmission electron cryo-microscopy and cryo-tomography to deduce the structure of mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles and Triton X-100. Time-resolved SAXS and dynamic light scattering were used to investigate the kinetics of the process. Findings Upon addition of moderate detergent amounts at low temperatures, the lipid vesicles implode into ordered rippled bilamellar disc structures. The bilayers arrange in a ripple phase to accommodate packing constraints caused by inserted TX-100 molecules. The collapse is suggested to occur through a combination of water structure destabilization by detergents flipping across the membrane and osmotic pressure causing interbilayer attraction internally. The subsequently induced ripples then stabilize the aggregates and prevent solubilization, supported by the observation that negatively charged vesicles undergo a different pathway upon TX-100 addition, forming large bicelles. The findings demonstrate the richness in assembly pathways of simple lipids and detergents and stimulate considerations for the use of certain detergents in membrane solubilization.

• König, Nico; Szostak, Szymon Mikolaj; Nielsen, Josefine Eilsø; Dunbar, Martha; Yang, Su & Chen, Weike [Show all 13 contributors for this article] (2023). Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers. ACS Nano. ISSN 1936-0851. 17(13), p. 12394–12408. doi: 10.1021/acsnano.3c01811. Full text in Research Archive Show summary

  Often nanostructures formed by self-assembly of small molecules based on hydrophobic interactions are rather unstable, causing morphological changes or even dissolution when exposed to changes in aqueous media. In contrast, peptides offer precise control of the nanostructure through a range of molecular interactions where physical stability can be engineered in and, to a certain extent, decoupled from size via rational design. Here, we investigate a family of peptides that form beta-sheet nanofibers and demonstrate a remarkable physical stability even after attachment of poly(ethylene glycol). We employed small-angle neutron/X-ray scattering, circular dichroism spectroscopy, and molecular dynamics simulation techniques to investigate the detailed nanostructure, stability, and molecular exchange. The results for the most stable sequence did not reveal any structural alterations or unimer exchange for temperatures up to 85 °C in the biologically relevant pH range. Only under severe mechanical perturbation (i.e., tip sonication) would the fibers break up, which is reflected in a very high activation barrier for unimer exchange of ∼320 kJ/mol extracted from simulations. The results give important insight into the relation between molecular structure and stability of peptide nanostructure that is important for, e.g., biomedical applications.

• Lone, Abdullah; Nielsen, Josefine Eilsø; Thulstrup, Peter W.; Lund, Reidar; Hansen, Paul Robert & Jenssen, Håvard (2022). Cyclic N-locked indolicidin analogues with antimicrobial activity: Effect of ring size and fatty acid acylation. European Journal of Medicinal Chemistry Reports. ISSN 2772-4174. 6. doi: 10.1016/j.ejmcr.2022.100080. Full text in Research Archive
• Nielsen, Josefine Eilsø; Alford, Morgan Ashley; Yung, Deborah Bow Yue; Molchanova, Natalia; Fortkort, John A. & Lin, Jennifer S. [Show all 12 contributors for this article] (2021). Self-Assembly of Antimicrobial Peptoids Impacts Their Biological Effects on ESKAPE Bacterial Pathogens. ACS Infectious Diseases. doi: 10.1021/acsinfecdis.1c00536. Full text in Research Archive
• Royes, J.; Bjørnestad, Victoria Ariel; Brun, G.; Narayanan, T.; Lund, Reidar & Tribet, C. (2021). Transition kinetics of mixed lipid:photosurfactant assemblies studied by time-resolved small angle X-ray scattering. Journal of Colloid and Interface Science. ISSN 0021-9797. doi: 10.1016/j.jcis.2021.11.133. Full text in Research Archive
• Nielsen, Josefine Eilsø; Prévost, Sylvain François; Jenssen, Håvard & Lund, Reidar (2021). Impact of antimicrobial peptides on: E. coli -mimicking lipid model membranes: Correlating structural and dynamic effects using scattering methods. Faraday discussions. ISSN 1359-6640. 232, p. 203–217. doi: 10.1039/d0fd00046a. Full text in Research Archive
• Bjørnestad, Victoria Ariel; Rydmark, Marcella Christine Orwick & Lund, Reidar (2021). Understanding the Structural Pathways for Lipid Nanodisc Formation: How Styrene Maleic Acid Copolymers Induce Membrane Fracture and Disc Formation. Langmuir. ISSN 0743-7463. 37(20), p. 6178–6188. doi: 10.1021/acs.langmuir.1c00304. Full text in Research Archive Show summary

  Lipid nanodiscs formed by mixtures of styrene maleic acid (SMA) copolymers and lipid membranes are important tools for studying membrane proteins in many biotechnological applications. However, molecular interactions leading up to their formation are not well understood. Here, we elucidate the nanodisc formation pathways for SMA/lipid vesicle mixtures using small-angle X-ray scattering (SAXS) that allows detailed in situ nanostructural information. SMA copolymer that is initially aggregated in solution inserts its styrene units into the lipid bilayer hydrocarbon region, leading to fractures in the membrane. The initial copolymer–lipid interactions observed in the vesicles are also present in the formed discs, with excess copolymer distributed along the normal of the bilayer. The size and SMA distribution in the resulting discs strongly depend on the temperature, lipid/copolymer ratio, and lipid type. We find that the solubilization limit increases for membranes above the melting point, suggesting that defects in gel-like lipid membranes play a significant role in membrane fracturing and nanodisc formation. These findings provide unique insights into the formation of nanodiscs as well as into the microscopic mechanism of solubilization, which plays an important role in many applications and products ranging from household goods to biotechnology and medicine.

• Nielsen, Josefine Eilsø & Lund, Reidar (2021). Molecular Transport and Growth of Lipid Vesicles Exposed to Antimicrobial Peptides. Langmuir. ISSN 0743-7463. 38(1), p. 374–384. doi: 10.1021/acs.langmuir.1c02736. Full text in Research Archive Show summary

  It is well-known that lipids constituting the cytoplasmic membrane undergo continuous reorganization to maintain the appropriate composition important for the integrity of the cell. The transport of lipids is controlled by mainly membrane proteins, but also spontaneous lipid transport between leaflets, lipid “flip–flop”, occurs. These processes do not only occur spontaneously under equilibrium, but also promote structural rearrangements, morphological transitions, and growth processes. It has previously been shown that intravesicular lipid “flip–flop” and intervesicular lipid exchange under equilibrium can be deduced indirectly from contrast variation time-resolved small-angle neutron scattering (TR-SANS) where the molecules are “tagged” using hydrogen/deuterium (H/D) substitution. In this work, we show that this technique can be extended to simultaneously detect changes in the growth and the lipid “flip–flop” and exchange rates induced by a peptide additive on lipid vesicles consisting of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), d-DMPC (1,2-dimyristoyl-d54-sn-glycero-3-phosphocholine), DMPG (1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol)), and small amounts of DMPE-PEG (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]). Changes in the overall size were independently monitored using dynamic light scattering (DLS). We find that the antimicrobial peptide, indolicidin, accelerates lipid transport and additionally induces limited vesicular growth. Moreover, in TR-SANS experiments using partially labeled lipid mixtures to separately study the kinetics of the lipid components, we show that, whereas peptide addition affects both lipids similarly, DMPG exhibits faster kinetics. We find that vesicular growth is mainly associated with peptide-mediated lipid reorganization that only slightly affects the overall exchange kinetics. This is confirmed by a TR-SANS experiment of vesicles preincubated with peptide showing that after pre-equilibration the kinetics are only slightly slower.

• König, Nico; Willner, Lutz; Pipich, Vitaliy; Mahmoudi, Najet & Lund, Reidar (2020). Tale of Two Tails: Molecular Exchange Kinetics of Telechelic Polymer Micelles. Physical Review Letters. ISSN 0031-9007. 124(19). doi: 10.1103/PhysRevLett.124.197801. Full text in Research Archive Show summary

  Telechelic polymers contain two chain ends that are able to promote self-assembly into “flowerlike” or interconnected micellar structures. Here, we investigate the molecular exchange kinetics of such micelles using time-resolved small-angle neutron scattering. We show that the activation energies of monofunctional and telechelic chain exchange are identical. This demonstrates that the two chain ends are not simultaneously released in a single event. Instead, the results show that, contrary to regular micelles, the kinetics occurs in a multistep process involving a collision-induced single-molecule exchange mechanism where the exchange rate is directly proportional to the polymer concentration. We show that this novel mechanism can be quantitatively explained by a simple kinetic model.

• Myhre, Synne; Amann, Matthias; Willner, Lutz; Knudsen, Kenneth Dahl & Lund, Reidar (2020). How detergents dissolve polymeric micelles: Kinetic pathways of hybrid micelle formation in SDS and block copolymer mixtures. Langmuir. ISSN 0743-7463. 36(43), p. 12887–12899. doi: 10.1021/acs.langmuir.0c02123. Full text in Research Archive Show summary

  Mixtures of amphiphilic polymers and surfactants are used in a wide range of applications, e.g., pharmaceuticals, detergents, cosmetics, and drug delivery systems. Still, many questions remain on how the structure and, in particular, the kinetics of block copolymer micelles are affected in the presence of surfactants and what controls the solubilization kinetics. In this work, we have studied the stability and solubilization kinetics of block copolymer micelles upon the addition of the surfactant sodium dodecyl sulfate (SDS) using small-angle X-ray/neutron scattering. The ability of the surfactant to dissolve polymer micelles or form mixed micelles has been investigated using two types of amphiphilic polymers, poly(ethylene-alt-propylene)–poly(ethylene oxide) (PEP1-PEO20) and n-alkyl-functionalized PEO (C28-PEO5). The exchange kinetics of C28-PEO5 micelles are in the order of hours, while PEP1-PEO20 micelles are known to be frozen on a practical timescale. In this work, we show that the addition of SDS to PEP1-PEO20 provides virtually no solubilization, even after an extended period of time. However, upon adding SDS to C28-PEO5 micelles, we observe micellar dissolution and formation of mixed micelles occurring on the timescale of hours. Using a coexistence model of mixed and neat micelles, the SAXS data were analyzed to provide detailed structural parameters over time. First, we observe a fast fragmentation/fission step followed by a slow reorganization process. The latter process is essentially independent of concentration at low volume fraction but is greatly accelerated at larger concentrations. This might indicate a crossover from a predominance of molecular exchange to fusion/fission processes.

• Schäfer, Ken; Kolli, Hima Bindu; Christensen, Mikkel Killingmoe; Bore, Sigbjørn Løland; Diezemann, Gregor & Gauss, Jürgen [Show all 9 contributors for this article] (2020). Supramolecular Packing Drives Morphological Transitions of Charged Surfactant Micelles. Angewandte Chemie International Edition. ISSN 1433-7851. 59(42), p. 18591–18598. doi: 10.1002/anie.202004522. Full text in Research Archive Show summary

  The shape and size of self‐assembled structures upon local organization of their molecular building blocks are hard to predict in the presence of long‐range interactions. Combining small‐angle X‐ray/neutron scattering data, theoretical modelling, and computer simulations, sodium dodecyl sulfate (SDS), over a broad range of concentrations and ionic strengths, was investigated. Computer simulations indicate that micellar shape changes are associated with different binding of the counterions. By employing a toy model based on point charges on a surface, and comparing it to experiments and simulations, it is demonstrated that the observed morphological changes are caused by symmetry breaking of the irreducible building blocks, with the formation of transient surfactant dimers mediated by the counterions that promote the stabilization of cylindrical instead of spherical micelles. The present model is of general applicability and can be extended to all systems controlled by the presence of mobile charges.

• König, Nico; Willner, Lutz; Carlström, Göran; Zinn, Thomas; Knudsen, Kenneth Dahl & Rise, Frode [Show all 8 contributors for this article] (2020). Spherical Micelles with Nonspherical Cores: Effect of Chain Packing on the Micellar Shape. Macromolecules. ISSN 0024-9297. 53(23), p. 10686–10698. doi: 10.1021/acs.macromol.0c01936. Full text in Research Archive Show summary

  Self-assembly of amphiphilic polymers into micelles is an archetypical example of a “self-confined” system due to the formation of micellar cores with dimensions of a few nanometers. In this work, we investigate the chain packing and resulting shape of Cn-PEOx micelles with semicrystalline cores using small/wide-angle X-ray scattering (SAXS/WAXS), contrast-variation small-angle neutron scattering (SANS), and nuclear magnetic resonance spectroscopy (NMR). Interestingly, the n-alkyl chains adopt a rotator-like conformation and pack into prolate ellipses (axial ratio ϵ ≈ 0.5) in the “crystalline” region and abruptly arrange into a more spheroidal shape (ϵ ≈ 0.7) above the melting point. We attribute the distorted spherical shape above the melting point to thermal fluctuations and intrinsic rigidity of the n-alkyl blocks. We also find evidence for a thin dehydrated PEO layer (≤1 nm) close to the micellar core. The results provide substantial insight into the interplay between crystallinity and molecular packing in confinement and the resulting overall micellar shape.

• Nam, Ho Yeon; Choi, Jieun; Kumar, S. Dinesh; Nielsen, Josefine Eilsø; Kyeong, Minkyo & Wang, Sungrok [Show all 15 contributors for this article] (2020). Helicity Modulation Improves the Selectivity of Antimicrobial Peptoids. ACS Infectious Diseases. 6(10), p. 2732–2744. doi: 10.1021/acsinfecdis.0c00356. Full text in Research Archive
• Nielsen, Josefine Eilsø; König, Nico; Yang, Su; Skoda, Maximilian W. A.; Maestro, Armando & Dong, He [Show all 8 contributors for this article] (2020). Lipid membrane interactions of self-assembling antimicrobial nanofibers: effect of PEGylation. RSC Advances. 10(58), p. 35329–35340. doi: 10.1039/d0ra07679a. Full text in Research Archive
• Nielsen, Josefine Eilsø; Bjørnestad, Victoria Ariel; Pipich, Vitaliy; Jenssen, Håvard & Lund, Reidar (2020). Beyond structural models for the mode of action: How natural antimicrobial peptides affect lipid transport. Journal of Colloid and Interface Science. ISSN 0021-9797. 582, p. 793–802. doi: 10.1016/j.jcis.2020.08.094. Full text in Research Archive Show summary

  Hypothesis: Most textbook models for antimicrobial peptides (AMP) mode of action are focused on structural effects and pore formation in lipid membranes, while these deformations have been shown to require high concentrations of peptide bound to the membrane. Even insertion of low amounts of peptides in the membrane is hypothesized to affect the transmembrane transport of lipids, which may play a key role in the peptide effect on membranes. Experiments: Here we combine state-of-the-art small angle X-ray/neutron scattering (SAXS/SANS) techniques to systematically study the effect of a broad selection of natural AMPs on lipid membranes. Our approach enables us to relate the structural interactions, effects on lipid exchange processes, and thermodynamic parameters, directly in the same model system. Findings: The studied peptides, indolicidin, aurein 1.2, magainin II, cecropin A and LL-37 all cause a general acceleration of essential lipid transport processes, without necessarily altering the overall structure of the lipid membranes or creating organized pore-like structures. We observe rapid scrambling of the lipid composition associated with enhanced lipid transport which may trigger lethal signaling processes and enhance ion transport. The reported membrane effects provide a plausible canonical mechanism of AMP-membrane interaction and can reconcile many of the previously observed effects of AMPs on bacterial membranes.

• Molchanova, Natalia; Nielsen, Josefine Eilsø; Sørensen, Kristian B; Krishna, Bala; Hansen, Paul Robert & Lund, Reidar [Show all 8 contributors for this article] (2020). Halogenation as a tool to tune antimicrobial activity of peptoids. Scientific Reports. 10(1). doi: 10.1038/s41598-020-71771-8. Full text in Research Archive Show summary

  Abstract Antimicrobial peptides have attracted considerable interest as potential new class of antibiotics against multi-drug resistant bacteria. However, their therapeutic potential is limited, in part due to susceptibility towards enzymatic degradation and low bioavailability. Peptoids (oligomers of N -substituted glycines) demonstrate proteolytic stability and better bioavailability than corresponding peptides while in many cases retaining antibacterial activity. In this study, we synthesized a library of 36 peptoids containing fluorine, chlorine, bromine and iodine atoms, which vary by length and level of halogen substitution in position 4 of the phenyl rings. As we observed a clear correlation between halogenation of an inactive model peptoid and its increased antimicrobial activity, we designed chlorinated and brominated analogues of a known peptoid and its shorter counterpart. Short brominated analogues displayed up to 32-fold increase of the activity against S. aureus and 16- to 64-fold against E. coli and P. aeruginosa alongside reduced cytotoxicity. The biological effect of halogens seems to be linked to the relative hydrophobicity and self-assembly properties of the compounds. By small angle X-ray scattering (SAXS) we have demontrated how the self-assembled structures are dependent on the size of the halogen, degree of substitution and length of the peptoid, and correlated these features to their activity.

• Fabia, Sandra Rodriguez; Øyen, Marita; Winter-Hjelm, Nicolai; Norrman, Jens; Lund, Reidar & Sørland, Geir [Show all 9 contributors for this article] (2020). Absorption of CO2 in lyotropic liquid crystals. Molecular Crystals and Liquid Crystals (MCLC). ISSN 1542-1406. 703(1), p. 87–106. doi: 10.1080/15421406.2020.1780830. Full text in Research Archive Show summary

  Vapor–liquid equilibria data of three poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)/water liquid crystals (LCs) with CO2 has been obtained up to 6 bar. The investigated LCs consist of 60% (EO)3(PO)50(EO)3 (Pluronic L81), 70% (EO)8(PO)47(EO)8 (Pluronic L92), and 70% L92-NH2. The maximum CO2 loading of the LCs was 5–13 g CO2/kg sample. Pure L81 and L92 displayed higher absorption of CO2 than the LCs. Rheology measurements revealed that the increasing viscosity of the samples decreases the CO2 loading. Water diffusion in the LCs was qualitatively investigated by nuclear magnetic resonance, confirming that free water and tightly bound water are present in the LCs.

• Amann, Matthias; Diget, Jakob Stensgaard; Lyngsø, Jeppe; Pedersen, Jan Skov; Narayanan, Theyencheri & Lund, Reidar (2019). Kinetic Pathways for Polyelectrolyte Coacervate Micelle Formation Revealed by Time-Resolved Synchrotron SAXS. Macromolecules. ISSN 0024-9297. 52(21), p. 8227–8237. doi: 10.1021/acs.macromol.9b01072. Full text in Research Archive
• Guyse, Joachim F. R. Van; Rosa, Victor R. De La; Lund, Reidar; Bruyne, Michiel De; Rycke, Riet De & Filippov, Sergey K. [Show all 7 contributors for this article] (2019). Striking Effect of Polymer End-Group on C60 Nanoparticle Formation by High Shear Vibrational Milling with Alkyne-Functionalized Poly(2-oxazoline)s. ACS Macro Letters. 8(2), p. 172–176. doi: 10.1021/acsmacrolett.8b00998. Full text in Research Archive
• Maric, Selma; Lind, Tania Kjellerup; Raida, Manfred Roman; Bengtsson, Eva-Lena; Fredrikson, Gunilla Nordin & Rogers, Sarah [Show all 14 contributors for this article] (2019). Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes. Scientific Reports. 9(1). doi: 10.1038/s41598-019-43713-6. Full text in Research Archive
• König, Nico; Willner, Lutz; Pipich, Vitaliy; Zinn, Thomas & Lund, Reidar (2019). Cooperativity during Melting and Molecular Exchange in Micelles with Crystalline Cores. Physical Review Letters. ISSN 0031-9007. 122(7). doi: 10.1103/PhysRevLett.122.078001. Full text in Research Archive Show summary

  Molecular exchange processes are important equilibration and transport mechanisms in both synthetic and biological self-assembled systems such as micelles, vesicles, and membranes. Still, these processes are not entirely understood, in particular the effect of crystallinity and the interplay between cooperative melting processes and chain exchange. Here we focus on a set of simple polymer micelles formed by binary mixtures of poly(ethylene oxide)-mono- n -alkyl-ethers ( C n − PEO 5 ) which allows the melting point to be tuned over a wide range. We show that the melting transition is cooperative in the confined 4–5 nm micellar core, whereas the exchange process is widely decoupled and unimeric in nature. As confirmed by differential scanning calorimetry, the total activation energy for ejecting a molecule out of the micellar core below the melting point is the sum of the enthalpy of fusion and the corresponding activation energy in the melt state. This suggests that a “local, single-chain melting process” preludes the molecular diffusion out of the micelle during chain exchange.

• Lone, Abdullah; Thomsen, Thomas T; Nielsen, Josefine Eilsø; Thulstrup, Peter W; Klitgaard, Rasmus N & Løbner-Olesen, Anders [Show all 9 contributors for this article] (2019). Structure-activity study of an all-D antimicrobial octapeptide D2D. Molecules. ISSN 1431-5157. 24(24). doi: 10.3390/molecules24244571. Full text in Research Archive
• König, Nico; Willner, Lutz & Lund, Reidar (2019). Structure and thermodynamics of mixed polymeric micelles with crystalline cores: Tuning properties: Via co-assembly. Soft Matter. ISSN 1744-683X. 15(39), p. 7777–7786. doi: 10.1039/c9sm01452g. Full text in Research Archive
• Nielsen, Josefine Eilsø; Lind, Tania Kjellerup; Lone, Abdullah; Gerelli, Yuri; Hansen, Paul Robert & Jenssen, Håvard [Show all 8 contributors for this article] (2019). A biophysical study of the interactions between the antimicrobial peptide indolicidin and lipid model systems. Biochimica et Biophysica Acta - Biomembranes. ISSN 0005-2736. 1861(7), p. 1355–1364. doi: 10.1016/j.bbamem.2019.04.003. Full text in Research Archive Show summary

  The naturally occurring peptide indolicidin from bovine neutrophils exhibits strong biological activity against a broad spectrum of microorganisms. This is believed to arise from selective interactions with the negatively charged cytoplasmic lipid membrane found in bacteria. We have investigated the peptide interaction with supported lipid model membranes using a combination of complementary surface sensitive techniques: neutron reflectometry (NR), atomic force microscopy (AFM), and quartz crystal microbalance with dissipation monitoring (QCM-D). The data are compared with small-angle X-ray scattering (SAXS) results obtained with lipid vesicle/peptide solutions. The peptide membrane interaction is shown to be significantly concentration dependent. At low concentrations, the peptide inserts at the outer leaflet in the interface between the headgroup and tail core. Insertion of the peptide results in a slight decrease in the lipid packing order of the bilayer, although not sufficient to cause membrane thinning. By increasing the indolicidin concentration well above the physiologically relevant conditions, a deeper penetration of the peptide into the bilayer and subsequent lipid removal take place, resulting in a slight membrane thinning. The results suggest that indolicidin induces lipid removal and that mixed indolicidin-lipid patches form on top of the supported lipid bilayers. Based on the work presented using model membranes, indolicidin seems to act through the interfacial activity model rather than through the formation of stable pores.

• Diget, Jakob Stensgaard; Lund, Reidar; Nyström, Bo; Wintgens, Veronique; Amiel, Catherine & Wimmer, Reinhard [Show all 7 contributors for this article] (2019). Self-assembled nanoparticles based on cyclodextrin-modified pullulan: Synthesis, and structural characterization using SAXS. Carbohydrate Polymers. ISSN 0144-8617. 213, p. 403–410. doi: 10.1016/j.carbpol.2019.01.106. Full text in Research Archive
• Nielsen, Josefine Eilsø; Bjørnestad, Victoria Ariel & Lund, Reidar (2018). Resolving the structural interactions between antimicrobial peptides and lipid membranes using small-angle scattering methods: The case of indolicidin. Soft Matter. ISSN 1744-683X. 14(43), p. 8750–8763. doi: 10.1039/c8sm01888j. Full text in Research Archive
• Jiang, Linhai; Yang, Su; Lund, Reidar & Dong, He (2018). Shape-specific nanostructured protein mimics from: De novo designed chimeric peptides. Biomaterials Science. ISSN 2047-4830. 6(2), p. 272–279. doi: 10.1039/c7bm00906b. Full text in Research Archive
• Schweikle, Manuel; Zinn, Thomas; Lund, Reidar & Tiainen, Hanna (2018). Injectable synthetic hydrogel for bone regeneration: Physicochemical characterisation of a high and a low pH gelling system. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 90, p. 67–76. doi: 10.1016/j.msec.2018.04.049. Full text in Research Archive Show summary

  Hybrid poly(ethylene glycol)-co-peptide hydrogels are a versatile platform for bone regeneration. For the use as injectable scaffolds, a good understanding of reaction kinetics and physical properties is vital. However, these factors have not yet been comprehensively illuminated. We show that gelation time can be effectively controlled by pH without affecting the elasticity of the formed hydrogels. Maleimide functionalised PEG gels at lower pH and produces more densely cross-linked networks than vinylsulfone functionalised PEG. Both form non-ideal networks. The elastic moduli on the order of a few kPa are in good agreement with the structural characterisation. Primary human osteoblasts cultured in proximity to bulk gels were not adversely affected in vitro. The results demonstrate that hybrid PEG-peptide hydrogels can be tailored to the requirements of in situ gelation. Attributed to their increased structural properties and a higher tolerance towards low pH, maleimide functionalised hydrogels might provide a better alternative for injectable applications.

• Trousil, Jiří; Filippov, Sergey K.; Hrubý, Martin; Mazel, Tomáš; Syrová, Zdeňka & Cmarko, Dusan [Show all 15 contributors for this article] (2017). System with embedded drug release and nanoparticle degradation sensor showing efficient rifampicin delivery into macrophages. Nanomedicine: Nanotechnology, Biology and Medicine. ISSN 1549-9634. 13, p. 307–315. doi: 10.1016/j.nano.2016.08.031. Full text in Research Archive
• Narayanan, Theyencheri; Wacklin, Hanna; Konovalov, Oleg & Lund, Reidar (2017). Recent applications of synchrotron radiation and neutrons in the study of soft matter. Crystallography Reviews. ISSN 0889-311X. 23(3), p. 160–226. doi: 10.1080/0889311X.2016.1277212. Full text in Research Archive
• Zinn, Thomas; Willner, Lutz; Knudsen, Kenneth & Lund, Reidar (2017). Self-assembly of mixtures of telechelic and monofunctional amphiphilic polymers in water: from clusters to flowerlike micelles. Macromolecules. ISSN 0024-9297. 50(18), p. 7321–7332. doi: 10.1021/acs.macromol.7b01501. Full text in Research Archive

View all works in NVA

• Cezar, Henrique Musseli; Bjørnestad, Victoria Ariel; Lund, Reidar & Cascella, Michele (2024). Metainference simulations to interpret small-angle scattering experiments of non-conventional surfactants. Full text in Research Archive
• Cezar, Henrique Musseli; Bjørnestad, Victoria Ariel; Lund, Reidar & Cascella, Michele (2024). Metainference simulations to interpret small angle scattering experiments of non-conventional surfactants. Full text in Research Archive
• Cezar, Henrique Musseli; Bjørnestad, Victoria Ariel; Lund, Reidar & Cascella, Michele (2024). Metainference simulations to interpret small angle scattering experiments. Full text in Research Archive
• Cezar, Henrique Musseli; Bjørnestad, Victoria Ariel; Prévost, Sylvain François; Lund, Reidar & Cascella, Michele (2024). Metainference simulations to interpret small angle scattering experiments. Full text in Research Archive
• Muthukamatchi, Anu; Lund, Reidar; Alcock, Benjamin; Ansaloni, Luca & Peters, Thijs (2024). Characterisation and Performance Evaluation of Elastomers for Carbon Capture and Storage Infrastructure: A Focus on CO2 Transportation. Full text in Research Archive
• Uggerud, Nora; Comerford, James & Lund, Reidar (2023). Functionalized aromatic bio-monomers for polyester synthesis. Full text in Research Archive
• Meuskens, Ina; Kristiansen, Per Eugen; Bardiaux, Benjamin; Koynarev, Vladimir Rosenov; Hatlem, Daniel & Prydz, Kristian [Show all 9 contributors for this article] (2023). Strain variations in a bacterial adhesin lead to different binding partners in the pathogen Yersinia enterocolitica. Full text in Research Archive
• Muthukamatchi, Anu; Lund, Reidar; Alcock, Benjamin; Ansaloni, Luca & Peters, Thijs (2023). Experimental characterization of elastomers for the CO2 transport applications. Full text in Research Archive
• Muthukamatchi, Anu; Lund, Reidar; Alcock, Benjamin; Ansaloni, Luca & Peters, Thijs (2022). Polymer materials for CO2 transport applications. Full text in Research Archive
• Moe, Harald; Lundanes, Elsa; Wilson, Steven Ray Haakon; Lund, Reidar & Røberg-Larsen, Hanne (2021). Releasing anitmicrobial peptides through liposomal nanocarriers to fight multidrug-resistant bacteria. Full text in Research Archive
• Lund, Reidar & Cascella, Michele (2021). Aggregation kinetics and photodynamics of photocontrollable surfactant AzoTMA: a molecular dynamics study. Full text in Research Archive
• Laurati, Marco & Lund, Reidar (2021). Interactions of non-ionic detergents with lipid membranes. Full text in Research Archive
• Sørensen, Henrik Vinther; Bjerregaard-Andersen, Kaare; Vaaje-Kolstad, Gustav; Krengel, Ute & Lund, Reidar (2020). Applying soft matter techniques to understand bacterial colonization. Full text in Research Archive
• Sørensen, Henrik Vinther; Krengel, Ute; Lund, Reidar; Browning, Kathryn & Bjerregaard-Andersen, Kaare (2019). Bacterial colonization investigated with X-ray and neutron techniques. Full text in Research Archive
• Bjørnestad, Victoria Ariel & Lund, Reidar (2019). The kinetic pathways of the solubilisation of lipid membranes by detergents seen by SAXS. Full text in Research Archive
• Sørensen, Henrik Vinther; Browning, Kathryn; Bjerregaard-Andersen, Kaare; Lund, Reidar & Krengel, Ute (2019). Applying X-rays and neutrons to understand a bacterial virulence factor. Full text in Research Archive
• Sørensen, Henrik Vinther; Krengel, Ute; Vaaje-Kolstad, Gustav; Lund, Reidar; Browning, Kathryn & Bjerregaard-Andersen, Kaare [Show all 7 contributors for this article] (2019). Using X-rays and neutrons to understand a bacterial colonization factor. Full text in Research Archive
• Sørensen, Henrik Vinther; Krengel, Ute; Browning, Kathryn; Bjerregaard-Andersen, Kaare; Cardenas, Marite & Lund, Reidar [Show all 7 contributors for this article] (2019). Study of bacterial colonization with X-ray and neutron scattering techniques. Full text in Research Archive
• Sørensen, Henrik Vinther; Browning, Kathryn; Bjerregaard-Andersen, Kaare; Lund, Reidar & Krengel, Ute (2018). Borrowing material science techniques to study biological problems. Full text in Research Archive
• Sørensen, Henrik Vinther; Browning, Kathryn L.; Lund, Reidar; Krengel, Ute & Bjerregaard-Andersen, Kaare (2018). A surface active enzyme and colonization factor investigated by x-ray and neutron scattering. Full text in Research Archive
• Sørensen, Henrik Vinther; Browning, Kathryn; Lund, Reidar; Bjerregaard-Andersen, Kaare & Krengel, Ute (2018). A surface active enzyme and colonization factor investigated by x-ray and neutron techniques. Full text in Research Archive
• Sørensen, Henrik Vinther; Bjerregaard-Andersen, Kaare; Lund, Reidar & Krengel, Ute (2018). A bacterial colonization factor studied by X-ray and neutron techniques. Full text in Research Archive
• Schweikle, Manuel; Bjørnøy, Sindre Hove; Zinn, Thomas; Lund, Reidar; Sikorski, Pawel & Tiainen, Hanna (2017). In situ mineralising injectable hydrogels for bone repair. Full text in Research Archive
• Schweikle, Manuel; Zinn, Thomas; Lund, Reidar & Tiainen, Hanna (2017). Injectable hydrogel scaffold for regenerative treatment of peri-implantitis defects. Full text in Research Archive
• Muthukamatchi, Anu; Lund, Reidar; Alcock, Ben & Ansaloni, Luca (2025). Polymer Materials for CO2 Transport Applications. Universitetet i Oslo. Full text in Research Archive Show summary

  This thesis investigates the suitability of elastomeric materials for CO2 transport applications within Carbon Capture and Storage (CCS) infrastructure by examining their thermal, mechanical, and structural responses to CO2 exposure. The ability of these materials to maintain their performance under relevant CO2 transport conditions is essential for ensuring operational reliability. While elastomers are widely used in sealing applications due to their flexibility, resilience, and chemical resistance, their interaction with CO2 can result in plasticization, swelling, and irreversible alterations in their physical and mechanical properties. This thesis systematically evaluates the effects of CO2 exposure on different elastomer systems, identifying key parameters that influence their behavior in CCS environments. Article 1 focuses on Ethylene Propylene Diene Monomer (EPDM) elastomers, examining the influence of crosslinking density and carbon black content on CO2 uptake, permeability, diffusion behavior, and mechanical performance. To assess CO2 transport properties, permeation tests using the constant volume and variable pressure method are conducted, while differential scanning calorimetry (DSC) and tensile testing provide insights into the thermal and mechanical responses of the materials. This study evaluates how material parameters impact the behavior of EPDM compounds in CO2 environments, offering a detailed understanding of their suitability for CCS transport applications. Article 2 examines fluoroelastomers (FKMs), assessing the effects of fluorine content and carbon black loading on CO2-induced plasticization, compression set, and mechanical properties. Given the widespread use of FKMs in high-performance sealing applications, this study evaluates their structural integrity using wide-angle X-ray scattering (WAXS), along with physical and mechanical performance under relevant CO2 transport conditions. Article 3 investigates poly(epichlorohydrin-co-ethylene oxide-co-allyl glycidyl ether) (GECO) elastomers, focusing on how dual-filler systems, comprising carbon black (CB) and talc, differ from conventional CB filler alone in influencing CO2 uptake, desorption kinetics, and structural stability. Further structural characterization using WAXS and Fourier-transform infrared spectroscopy (FTIR) is conducted to analyze structural changes, while scanning electron microscopy (SEM) examines surface morphology alterations following rapid gas decompression (RGD). Article 4 investigates EPDM, Natural Rubber (NR), and Isobutylene Isoprene Rubber (IIR), focusing on their thermal, mechanical, and transport behavior under high-pressure CO2 exposure. Experimental methods include DSC, TGA, dilatometry, DMA, and gas sorption measurements. In addition, solubility and permeability are modeled using the Sanchez–Lacombe lattice fluid equation of state and the standard transport model in collaboration with research partners. The results show that EPDM exhibits low solubility and stable mechanical properties, while NR and IIR show more pronounced reductions in modulus during CO2 exposure. IIR also displays blistering after decompression, indicating reduced mechanical integrity under rapid depressurization conditions. By integrating these studies, this thesis provides a comprehensive evaluation of different elastomers considered as potential materials for CO2 transport applications due to their unique combination of properties. The findings contribute to a better understanding of how material parameters in compound formulations affect elastomer performance under CO2 transport conditions, providing valuable criteria for material selection and optimization in CCS infrastructure.

• Torjusen, Henrik & Lund, Reidar (2024). Complex Coacervation of Antimicrobial Peptides and Polymers: Controlling Drug Encapsulation and Micellar Size. Universitetet i Oslo. Full text in Research Archive Show summary

  Due to the escalating threat of the pathogens’ capability of quick adaptation to antibiotics, combined with the slow drug development over the past couple of decades, new alternatives are of great importance to minimize the deaths and morbidity connected to bacterial infections. Antimicrobial peptides (AMPs) serve as promising candidates due to their wide range of modes of action and their non-specific affinity against the cellular membrane. However, they are not widely applied in the medical industry due to several challenges, such as degradation, low bioavailability, and cytotoxicity. Thus, seeking suitable opportunities to overcome these challenges might advance the combat against antibiotic-resistant bacteria. Among the antimicrobial peptides under investigation, colistin emerges as a potent AMP despite its challenges in neurotoxicity and degradation. To tackle these issues, we adopted a novel approach, and used the well-established technique called complex coacervation to encapsulate colistin. This thesis presents a detailed exploration of the complex coacervation process using various types of the diblock copolymer poly(ethylene glycol)n-b-poly(methacrylic acid)m in combination with colistin. We aimed to explore its potential in reducing adverse side effects through strategic encapsulation while having full control of composition, size and stability. More specifically, the main goal was to develop a drug encapsulation system with controlled coacervation size, a truly innovative step in drug delivery systems. To obtain comprehensive insights into these properties, scattering techniques such as small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) were employed with analytical scattering models. These techniques offer precise particle size, composition, and structural characteristics analysis. The findings show successful encapsulation of colistin using several degrees of polymerization into complex coacervate micelles. The resulting micelles were found to have characteristics that are highly dependent on environmental changes such as pH, temperature, and salt present. Additionally, combining different degree of polymerization polymers precisely made size-tunable hybridized coacervates, facilitated size control ranging from radii of 10 nm to 100 nm. When these polymers were mixed prior to complexation, an extensive change in system characteristics was revealed compared to mixing individual coacervates to the same end state, indicating the presence of a kinetically controlled system. Accompanying this, the stability and size distribution of previously unstable particles was increased by hybridizing with a lower molecular weight polymer, making the micelles less susceptible to aggregation and displaying higher reproducibility. A clear trend in concentration dependency showed that the formation of complex coacervates at a lower concentration gave a more precise regulation of the polydispersity. Furthermore, the coacervation process was found to be optimized further by elevation of pH and temperature. This research holds immense potential in advancing drug delivery systems and in optimizing therapeutic efficacy. Moreover, the direct size control of the drug encapsulation as well as control of the compositional characteristics of the system could enhance the protection of several filtration pathways and increases circulation in the bloodstream. In addition, the results highlight the critical and beneficial use of model-dependent SAXS data analysis. These findings could potentially revolutionize the field of drug delivery, offering more effective and targeted treatments for bacterial infections in a new era of precision medicine.

• Solberg, Audny Lodden; Lund, Reidar & Koynarev, Vladimir Rosenov (2024). Characterization of well-defined poly(styrene maleic acid) and its solubilization of liposomes. Universitetet i Oslo. Full text in Research Archive
• Krogseth, Ola Bohne & Lund, Reidar (2023). The Effect of Antimicrobial Peptides on Ion Transport in Model Membranes. Universitetet i Oslo. Full text in Research Archive Show summary

  This thesis delves into the ion transport mechanisms of antimicrobial peptides through lipid membranes, examining the effects of peptide and saline concentrations on membrane properties such as structure, shape, and response to osmotic shock. To gain a comprehensive understanding, three distinct experimental approaches were utilized: scattering, electrophysiology, and imaging techniques. The work focus on using simple models roughly mimicking the negative surface of Gram-negative bacterial lipid membranes. These are used to decipher the ion transport capabilities of antimicrobial peptides and their ability in mitigating osmotic shock. Using an electrophysiology technique, specifically suspended planar lipid bilayers, allowed a direct method of detecting ion perturbations through the membrane upon peptide addition. The establishment of a suspended planar lipid bilayer lab, in addition to the development of a consistent protocol for producing functional lipid films, were essential to this research. The findings indicate that the peptide gramicidin forms a membrane-spanning pore, facilitating ion transport. Furthermore, it was found that indolicidin, another peptide, may appear to be involved in an ion-carrying mechanism. Additionally, the thesis demonstrate that small unilamellar liposomes containing water have a structural change under varying saline concentrations, which might be counterbalanced by the introduction of antimicrobial peptides. This discovery and further research could shed light on the capacity of peptides to transport ions across the membrane and alleviate osmotic pressure. This work employed small-angle X-ray scattering in tandem with electron microscopy and dynamic light scattering to explore the morphological changes of liposomes experiencing osmotic pressure. This investigation revealed the size and morphological alterations in liposomes was induced by osmotic pressure. It was found that osmotic shock causes liposomes to transition into a bilamellar structures. This morphological change was found to be alleviated through the ion transport facilitated by antimicrobial peptides.

• Bjørnestad, Victoria Ariel & Lund, Reidar (2023). Surfactant micelles and structural pathways for solubilization of lipid membranes. u. Full text in Research Archive
• Anor, Hannah Merlan & Lund, Reidar (2023). Developing polymer micelles conjugated with antimicrobial peptides. Universitetet i Oslo. Full text in Research Archive
• Ali, Lelaw Jalal & Lund, Reidar (2023). Delivering antimicrobial peptides through polymer complexation – creating efficient nanocarriers to fight resistant bacteria. Universitetet i Oslo. Full text in Research Archive Show summary

  Because of the limited number of antibiotics available and the similarities in their activity and mode of action, considerable nonclinical and clinical research is being spent in the discovery and development of new and non-conventional anti-infective medicines. Interestingly, the polymyxins have piqued the interest of researchers as promising new antibiotics to control infectious pathogens arising from MDR Gram-negative bacteria. In reality, only a few polymyxins have been utilized in “real-world” application, with the most clinically relevant being colistin. While efficacious in the clinical setting, there were subsequent studies that reported severe toxicities with use of colistin as a therapeutic option, especially nephrotoxicity and neurotoxicity as uncommon adverse event The disadvantages associated with colistin can be mitigated by encapsulating the peptide in nanocarriers like block copolymer micelles. However, there is a scarcity when it comes to core-shell assemblies by peptide-polymer conjugates, and in particular the assemblies of peptides assembled with neutral-polyanion DHBC. Moreover, the relation between the release of the peptide and the nanocarrier structure and dynamics is lacking. Therefore, the overall aim of the research presented in this thesis was to develop novel nanomedicines based on the peptide colistin. This includes a systematically investigation of the phase diagram of colistin/PEO-b-PMAA mixtures as a function of pH, charge ratio and total concentration. The overall goal will be to find optimal conditions under which stable core-shell colistin-polymer complexes are formed. In the second part of the project, different formulations of colistin-polymer nanoparticles where investigated in vitro for their bacterial killing activity against few multidrug-resistant Gram-negative bacteria isolates, which were compared to that of free colistin.

• Diget, Jakob Stensgaard; Nyström, Bo & Lund, Reidar (2022). In Pursuit of Well-Defined Organic Polymers - Controlled Synthesis and Accurate Characterization. Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Oslo. Full text in Research Archive Show summary

  Polymers are large (macro) molecules consisting of parts, or repeating units. The immense importance is reflected by the action of polynucleotides, e.g., DNA and RNA. As a result of their perfectly defined molecular structure, they direct the synthesis of all organic life forms. Well-defined synthetic polymers are gaining traction in fields such as biomedical science and the coatings industry, where their specific properties lead to more sophisticated materials. Not surprisingly, some of the most daunting and prestigious goals of polymer chemists, are to control the polymer molecular structure via synthesis and establish structure-property relationships. In this thesis, focus is on functional polyelectrolytes (charged chains) and polysaccharides (sugar chains), for potential use in biomedical science where specific and predictable properties are important. For the polymers in question, however, there is a lack of reliable controlled synthesis procedures and accurate characterization methods. The primary objective of the studies presented in this thesis has therefore been to establish such procedures and methods. As a secondary objective, specific scenarios (e.g., self-assembly and response to stimuli) have been investigated, and structure-property relationships thus elucidated. These new procedures and studies are expected to aid researchers in obtaining well-defined polymers with specific and predictable properties that may be used in, e.g., imaging, drug - and gene delivery systems, to combat diseases such as cancer.

• Spustova, Karolina; Gözen, Irep; Lund, Reidar & Carlson, Andreas (2021). Membranous Protocell Superstructures. Universitetet i Oslo. Full text in Research Archive Show summary

  How primitive cells emerged and developed on the early Earth remain an unsolved question. In contrast to the hypotheses that the first living cells evolved from a single ancestor, their development as colonies would provide numerous advantages, such as mechanical stability, enhancement of chemical reactions, and sharing of prebiotic molecules. In this PhD thesis, the formation and development of colony-like primitive cell structures and populations was investigated using three simple ingredients: water, fat molecules and solid surfaces. Transformation of fat agglomerates into large populations of structured primitive cells that are able to communicate and migrate, was observed under a light microscope. The role of solid surfaces which were abundant on the early Earth in form of rocks and minerals, was shown to be fundamental for these processes. These findings make us rethink the current theories on how life originated and show that solid surfaces might have played an important role in the emergence of primitive cells on the early Earth.

• Köksal, Elif; Gözen, Irep; Lund, Reidar & Carlson, Andreas (2021). Surface-assisted formation and development of model protocells. Universitetet i Oslo. Full text in Research Archive Show summary

  By enabling formation and development of primitive cells, also known as protocells, solid surfaces might have played an important role in the emergence of life on Earth. Current theories on how life originated from primitive cells are based on the initial step, where a spherical capsule made from fat molecules formed spontaneously in water. This model explains the formation well, but not the following steps, such as growth, replication and division. In this PhD thesis, the possible involvement of solid surfaces in the formation and development of primitive cells has been investigated. Solid surfaces existed in the form of rocks and minerals on the early Earth. By bringing together three simple ingredients: solid surfaces, fat molecules and water, and observing their interactions by means of microscopy, a series of unique transformations has been identified. Examples of such behavior are the formation of protocell networks connected with lipid nanotubes, formation of subcompartments similar to organelles in modern cells, protocell fusion and colony formation. Nano-engineered artificial surfaces, as well as natural surfaces including glasses, minerals, rocks, and a meteorite fragment from Mars originating from the earliest crust of the planet were used in the studies.

• Sørensen, Henrik Vinther; Krengel, Ute; Lund, Reidar & Bjerregaard, Kaare (2021). Of Shellfish and Men: Applying X-ray and neutron techniques to investigate surface-active bacterial colonization factors. Universitetet i Oslo, Det matematisk-naturvitenskapelige fakultet. Full text in Research Archive Show summary

  Bacteria responsible for diseases such as cholera and pneumonia form biofilms for surviving in the environment and inside their human hosts. The process involves enzymes that target sugars, providing the bacteria with nutrients. An in-depth understanding of the mechanisms of these enzymes can potentially lead to new vaccines, but also new means to convert complex sugars to clean energy sources. We used X-ray and neutron scattering methods to elucidate how these enzymes bind to chitin in the environment and how they degrade it. The work reveals new insight into the structures and mechanisms of the enzymes and how the bacteria use them to survive and thrive in the environment and inside humans.

• Moe, Harald Røsand; Wilson, Steven Ray Haakon; Lundanes, Elsa; Røberg-Larsen, Hanne & Lund, Reidar (2021). Establishing a liquid chromatography-mass spectrometry method for the quantification of colistin A, a last line of defense against antibiotic resistance. Universitetet i Oslo. Full text in Research Archive Show summary

  Antibiotic resistance has become an increasingly pressing issue in recent times. With a dwindling discovery rate of new antibacterials, gram-negative bacteria threaten to return humanity to the pre-antibiotic era where mere paper cuts could result in fatal outcomes. The antimicrobial peptide colistin is our present-day last line of defense against gram-negative infections. Nevertheless, despite the recent surge in use and research on colistin, research on its biological effects and chemical behavior remains somewhat scarce. Colistin was initially abandoned due to numerous reports of neuro- and nephrotoxicity. Slow leakage from colistin-loaded liposomes may reduce this toxicity significantly. In this work, an LC-MS method for separating and quantifying colistin and polymyxin B1 was developed to measure colistin leakage from loaded liposomes over time. Isocratic elution provided adequate separation of polymyxin E1 and the internal standard, polymyxin B1, and measurements were done using a triple-quadrupole MS. Widely unreported and uninvestigated adsorption and degradation mechanisms of colistin were observed and addressed by adding a 100 mM ammonium formate buffer at pH 3 to solutions of colistin. The LC-MS method provides a reliable and accurate approach for measuring colistin at lower concentrations (&lt; 10 µg/mL) in ammonium formate buffered solutions, and the future challenges and potential approaches for further research upon colistin are discussed. The LC-MS method described serves as a solid platform for further research on colistin, colistin toxicity negation, and more may be built upon.

• Porobic, Mirna; Lund, Reidar & Bjørnestad, Vicoria Ariel (2020). Mechanisms of vesicle solubilisation: Mapping the solubilisation mechanisms of DMPC liposomes by the detergents SDS and DDM using SAXS. Universitetet i Oslo. Full text in Research Archive
• Nielsen, Josefine Eilsø; Lund, Reidar; Knudsen, Kenneth Dahl & Jensen, Håvard (2020). Examining the Molecular Mechanism of Antimicrobial Peptides using Neutron and X-ray Scattering Techniques. Universitetet i Oslo. Full text in Research Archive Show summary

  Antimicrobial peptides (AMPs) are found in Nature as a part of the innate immune system in a wide range of species, including humans. Because of the emerging concern of widespread antibiotic resistance new antibiotics are of great importance. AMPs have attracted considerable interest, but the exact molecular mechanism of these compounds is still an object of debate. AMPs have been hypothesised to cause pore formation, membrane-solubilisation, or changes to the overall membrane structures. Here we combine small angle X-ray/neutron scattering techniques, and neutron reflectometry to systematically study the effect of a broad selection of AMPs on lipid membranes. Our results reveal a general peptide-induced acceleration of lipid transport processes, without changes to the overall membrane structure or creation of organised pores. Enhanced lipid transport can be linked with rapid scrambling of the lipid composition which may trigger lethal signalling processes, and enhance ion transport. The reported membrane effects provide a plausible canonical mechanism of AMP-membrane interaction and may reconcile previously observed effects of AMPs on bacterial membranes.

• Myhre, Synne & Lund, Reidar (2019). Studying the Kinetic Pathways for Micellar Solubilisation Using Small Angle Scattering Techniques: Interaction Between an Anionic Surfactant and Polymer Micelles. Universitetet i Oslo. Full text in Research Archive Show summary

  Polymer micelles can be used in pharmaceuticals, detergents, cosmetics and have a potential for drug delivery systems. In many applications of polymeric micelles, there are also surfactant molecules present. Still, it is an open question of how these affect the polymer micelles, and the present master thesis focuses on the interaction between polymeric micellar systems and surfactants. For example, the kinetic processes involved in mixtures of surfactants and block copolymer micelles are not well understood. It is commonly known that surfactants exhibit rather fast equilibration kinetics, in the order of micro- to milliseconds, while polymers are much slower, in the order of minutes to months. This master thesis is a study of the stability and solubilisation kinetics of block copolymers micelles upon addition of surfactant sodium dodecyl sulphate (SDS) using small-angle X-ray scattering (SAXS) and time-resolved small-angle neutron scattering (TR-SANS). The ability of the surfactant to dissolve polymer micelles or form mixed micelles has been investigated by using two types of amphiphilic polymers, poly(ethylene propylene)-poly(ethylene oxide) (PEP-PEO) and alkyl-functionalized PEO (C28-PEO5 and C21PEO5 ). The exchange kinetics of C21PEO5 micelles occurs over a few seconds, while for C28PEO5 micelles the chains exchange on time scales in the order of hours. Finally, PEP1-PEO20 micelles are known to be frozen on any practical time scales. In this work, we show that the addition of SDS to PEP1-PEO20 shows virtually no change, even after an extended period. However, using time-resolved SAXS, we observe micellar dissolution and formation of mixed micelles within hours, when adding SDS to C28PEO5. Noteworthy, upon the addition of SDS to C21PEO5, these processes occur within seconds. In addition, we found that the kinetics of formation of mixed micelles is accelerated with the amount of added surfactant for both C28PEO5 and C21PEO5. The measured scattering curves have been analyzed with a newly developed three-shell model consisting of an alkane core, an SDS head group shell, and a PEO corona, which was tested for the first time on this system. The polymer micelles are found to break down by two processes, one fast fragmentation reaction and one slow re-organisation step by unimer exchange, and, thus, is highly dependent on the length of the hydrophobic block.

• Christensen, Mikkel Killingmoe & Lund, Reidar (2019). Karakterisering av nanostrukturen og vannpermeabiliteten til selvassosierende systemer ved bruk av spredningsteknikker. Universitetet i Oslo. Full text in Research Archive Show summary

  Surfaktanter og kopolymerer er molekyler som kan selvassosiere på nanonivå til en rekke forskjellige strukturer. Dette kan være alt fra sfærer og sylindre, til bi-lag tilsvarende de som finnes i cellemembraner. Disse strukturene har mange viktige anvendelser som for eksempel surfaktanter i såpe og kosmetikk, til mer avanserte anvendelser som medisinbærere i nanomedisinsystemer. På bakgrunn av dette kan forskning på disse molekylene og strukturene være meget nyttig, og det er spesielt viktig å forstå hvordan de avhenger av forskjellige molekylære egenskaper og hvordan de påvirkes av endringer i eksterne parametere som temperatur, pH og salt. Ny forskning på dette feltet kan dermed brukes til å bedre forståelsen av den fundamentale termodynamikken til selvassosierende systemer og for å skreddersy disse til spesifikke anvendelser. Et av de mest viktige og velstuderte amfifile molekylene er den anioniske surfaktanten natriumdodecylsulfat (SDS). Denne surfaktanten danner globulære miceller i vandige lønsinger som er høyst sensitive til små endringer i eksterne parametere som temperatur, pH og ionestyrke. En interresant egenskap ved disse er at de i tilstedeværelse av salt forlenges og danner sylindriske miceller som kan nå nesten makroskopiske lengder. Selv om denne prosessen er velstudert, har ikke mekanismene bak denne overgangen blitt fullstendig beskrevet kvantitativt. Eksperimentelle resultater kan i kombinasjon med datasimuleringer bli brukt til å utvikle mer nøyaktige modeller for å beskrive detaljene rundt denne overgangen. Ved å bruke lav-vinkel røntgenspredning (SAXS) fra en synkrotronkilde i kombinasjon med analytiske modeller, ble globulær-til-sylinderovergangen i dette arbeidet karakterisert som en funksjon av ionestyrke med forskjellige salter (NaCl, MgCl2, KCl and CaCl2). Både NaCl og MgCl2 forårsaket en eksponentiell økning i konturlengden til micellenene som en funksjon av ionestyrke, mens KCl og CaCl2 forårsaket faseseparasjon. Fasediagrammer basert på disse resultatene viser overlapp mellom overgangsområdene ved bruk av ionestyrke for NaCl og MgCl2. Ved den høyeste konsentrasjonen av MgCl2 ble det i tillegg påvist lange, fleksible sylindre med mulig krysslinking og/eller forgrening av micellene. Det andre hovedemnet i dette arbeidet er diblokk-kopolypeptidene PBLG-PLL bestående av en hydrofobisk del av poly-γ-benzyl-L-glutamat (PBLG) og en hydrofil del av poly-L-lysin (PLL). Disse kopolypeptidene er forventet å produsere store vesikler i vandig løsning og er frem til nå ubeskrevet i litteraturen. Vesiklene ble studert ved å forsøke å tilpasse en analytisk modell for en vesikkelstruktur til SAXS-data basert på resultater fra dynamisk lysspredning (DLS) og transmisjonselektronmikroskopi (TEM). Selv om tegn til vesikler ble funnet med TEM, indikerte spredningseksperimentene tilstedeværelse av andre morfologier. Den strukturelle karakteriseringen av systemene ved bruk av en vesikkelmodell ble derfor mislykket. På tross av dette, ble spredningskurvene fra partiklene analysert kvalitativt, og partiklene ble funnet til å være eksepsjonelt stabile ved endringer av parametere som temperatur og ionestyrke, noe som er ønsket i mange anvendelser. Vanntransporten gjennom vesiklene ble også studert ved bruk av tidsoppløst lav-vinkelnøytronspredning (TR-SANS) for å måle permeabiliteten til membranene. En komplett utveksling av vann gjennom bi-laget skjedde her raskere enn tidsskalen som var tilgjengelig med det eksperimentelle oppsettet, noe som er bemerkelsesverdig og en utypisk egenskap ved kopolymermembraner.

• Bjørnestad, Victoria Ariel & Lund, Reidar (2018). Liposomes as a model system for the study of surface active peptides. Universitetet i Oslo. Full text in Research Archive

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