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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
.
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Muthukamatchi, Anu; Lund, Reidar; Alcock, Benjamin; Ansaloni, Luca & Peters, Thijs
(2023).
Experimental characterization of elastomers for the CO2 transport applications.
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Muthukamatchi, Anu; Lund, Reidar; Alcock, Benjamin; Ansaloni, Luca & Peters, Thijs
(2022).
Polymer materials for CO2 transport applications.
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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.
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Lund, Reidar & Cascella, Michele
(2021).
Aggregation kinetics and photodynamics of photocontrollable surfactant AzoTMA: a molecular dynamics study.
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Laurati, Marco & Lund, Reidar
(2021).
Interactions of non-ionic detergents with lipid membranes.
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Sørensen, Henrik Vinther; Bjerregaard-Andersen, Kaare; Vaaje-Kolstad, Gustav; Krengel, Ute & Lund, Reidar
(2020).
Applying soft matter techniques to understand bacterial colonization.
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Sørensen, Henrik Vinther; Krengel, Ute; Lund, Reidar; Browning, Kathryn & Bjerregaard-Andersen, Kaare
(2019).
Bacterial colonization investigated with X-ray and neutron techniques.
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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.
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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.
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Sørensen, Henrik Vinther; Browning, Kathryn; Bjerregaard-Andersen, Kaare; Lund, Reidar & Krengel, Ute
(2019).
Applying X-rays and neutrons to understand a bacterial virulence factor.
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Bjørnestad, Victoria Ariel & Lund, Reidar
(2019).
The kinetic pathways of the solubilisation of lipid membranes by detergents seen by SAXS.
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Sørensen, Henrik Vinther; Browning, Kathryn; Bjerregaard-Andersen, Kaare; Lund, Reidar & Krengel, Ute
(2018).
Borrowing material science techniques to study biological problems.
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Sørensen, Henrik Vinther; Bjerregaard-Andersen, Kaare; Lund, Reidar & Krengel, Ute
(2018).
A bacterial colonization factor studied by X-ray and neutron techniques.
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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.
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Sørensen, Henrik Vinther; L. Browning, Kathryn; Lund, Reidar; Krengel, Ute & Bjerregaard-Andersen, Kaare
(2018).
A surface active enzyme and colonization factor investigated by x-ray and neutron scattering.
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Sørensen, Henrik Vinther; Browning, Kathryn; Lund, Reidar; Bjerregaard-Andersen, Kaare & Krengel, Ute
(2017).
A surface active enzyme and colonization factor investigated by x-ray and neutron scattering - Hercules.
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Schweikle, Manuel; Bjørnøy, Sindre Hove; Zinn, Thomas; Lund, Reidar; Sikorski, Pawel & Tiainen, Hanna
(2017).
In situ mineralising injectable hydrogels for bone repair.
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Schweikle, Manuel; Zinn, Thomas; Lund, Reidar & Tiainen, Hanna
(2017).
Injectable hydrogel scaffold for regenerative treatment of peri-implantitis defects.
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Schweikle, Manuel; Bjørnøy, Sindre Hove; Zinn, Thomas; Lund, Reidar; Sikorski, Pawel & Tiainen, Hanna
(2017).
Mineralised injectable hydrogels for bone regeneration.
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Lund, Reidar
(2016).
The Natural Route to Complexity.
ESRF Newsletter.
ISSN 1011-9310.
74,
p. 16–17.
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Zinn, Thomas; Lund, Reidar; Willner, Lutz & Knudsen, Kenneth
(2016).
Structure and Kinetics of Telechelic Polymers.
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Zinn, Thomas; Lund, Reidar; Willner, Lutz; Richter, Dieter & Pipich, Viltaliy
(2016).
Confinement Effects and Molecular Exchange in Micelles with Partly Crystallised Cores.
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Zinn, Thomas; Lund, Reidar; Willner, Lutz; Pipich, Vitaliy & Richter, Dieter
(2015).
Chain exchange in polymeric micelles: Effect of core crystallization and conformational entropy.
Joint Annual Report 2015 of the MLZ and FRM II.
doi:
10.14459/2015md1292666.
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Zinn, Thomas; Lund, Reidar; Willner, Lutz; Lettinga, Pavlik & Kohlbrecher, Joachim
(2015).
Rheo-SANS study of reversible polymeric gels: shear-induced structure formation and melting.
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Zinn, Thomas; Lund, Reidar; Willner, Lutz; Richter, Dieter & Pipich, Vitaliy
(2015).
Crystallization in Micellar Cores: Melting Point Depression and Influence on Molecular Exchange Kinetics.
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Nyström, Bo; Bekhradnia, Sara; Naz, Iram; Lund, Reidar; Appelhans, Dietmar & Sande, Sverre Arne
(2015).
Structural features of maltose-functionalized hyperbranched poly(ethylene imine) and their complexes
.
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Tiainen, Hanna; Geissler, Sebastian; Lund, Reidar & Haugen, Håvard Jostein
(2015).
pH triggered aggregation of a structurally disordered polyproline peptide.
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Tiainen, Hanna; Geissler, Sebastian; Lund, Reidar & Haugen, Håvard Jostein
(2015).
pH triggered self-assembly and aggregation of a structurally disordered proline-rich polypeptide.
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Zinn, Thomas; Lund, Reidar & Willner, Lutz
(2015).
Crystallization within Micellar Cores Exhibit simple
Gibbs-Thomson Behaviour.
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Zinn, Thomas; Willner, Lutz & Lund, Reidar
(2015).
Core Crystallization and Kinetics of Polymeric Micelles
studied by SAS.
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Bjørnestad, Victoria Ariel & Lund, Reidar
(2023).
Surfactant micelles and structural pathways for solubilization of lipid membranes.
u.
ISSN 1501-7710.
2023(2603).
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Krogseth, Ola Bohne & Lund, Reidar
(2023).
The Effect of Antimicrobial Peptides on Ion Transport in Model Membranes.
Kjemisk Institutt, Universitetet i Oslo.
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.
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Jalal Ali, Lelaw & Lund, Reidar
(2023).
Delivering antimicrobial peptides through polymer complexation – creating efficient nanocarriers to fight resistant bacteria.
Kjemisk Institutt, Universitetet i Oslo.
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.
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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.
ISSN 1501-7710.
2022(2482).
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.
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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.
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 (< 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.
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Köksal, Elif; Gözen, Irep; Lund, Reidar & Carlson, Andreas
(2021).
Surface-assisted formation and development of model protocells.
Universitetet i Oslo, Det matematisk-naturvitenskapelige fakultet.
ISSN 1501-7710.
2021(2401).
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.
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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.
ISSN 1501-7710.
2021(2417).
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.
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Spustova, Karolina; Gözen, Irep; Lund, Reidar & Carlson, Andreas
(2021).
Membranous Protocell Superstructures.
Universitetet i Oslo, Det matematisk-naturvitenskapelige fakultet.
ISSN 1501-7710.
2021(2467).
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.
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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.
Show summary
Detergents are widelyused in daily life as in cleaning products and cosmetics, but also for pharmaceutical and biological purposes.In that regard the solubilisation of biological membranes for the extraction of proteins is important.This thesis looks at the solubilisation of 1,2-dimyristoyl-sn-glycero-3-phosphocholine(DMPC)liposomes by n-dodecyl β-D-maltoside(DDM)and sodium dodecyl sulphate (SDS)detergent micelles.The three-stage has been suggested as a model for explainingthe solubilisation of liposomes by detergents. It distinguishes between fast and slow solubilisation, largely believed to be controlled by the detergents ability to flip-flop through the lipid bilayer. SDS and DDM are both considered slow solubilisers thatare unableto flip-flop.
SAXS can be used to investigate the structure of particles in the size rangeof ahundred nanometres down to atomic resolution.In this thesis,SAXS was used to study the solubilisation of DMPC liposomes by SDS and DDMby measuring the individual detergents and liposomes and comparing these measurements to the mixtures of the detergents and liposomes at different concentrations and temperatures. The aim was to investigate the behaviour of the detergents and their mechanisms of solubilisation, and to see if the detergents act according to the three-stage model, and if not, how they deviate from it. The results are interpreted by using analytical modelsthat are fitted tothe scattering patternof the measurements.It was found that SDS solubilises DMPC in accordance with thethree-stage model. The solubilisation is gradual and involves insertion into the bilayer, followed by saturation of the bilayer, then a coexistencephase where mixed micelles and lipids both exist in solution, beforethe solution only containsmixed micelles that gradually become smaller with the increase of SDS concentration.
The DDMand DMPC mixturesshowed interesting behaviour.It was shown that DDM, though following a three-stage solubilisation mechanism, does have an intermediate stage where multilamellarliposomes are createdat low to moderate detergent concentrations.It seems also that the multilamellarity decreases with increasing concentration of DDM.Both detergents seem to solubilise DMPC faster when the liposomes were kept at 20C, this probably because of the phase shift to gel-phase that DMPC undergoes at 24C.There are howeverothersignificant differences between the two detergents. SDS seems to follow the solubilisation mechanism suggested by the three-stage model, while DDM has an intermediate stage where it creates multilamellar liposomes. DDM may cause the formation of multilamellar liposomes by inducing pore formation in theliposomemembrane. The thesis highlights the differences between SDS and DDM in liposome solubilisation, which may aid further studies choose the most suited detergent for liposome solubilisation in cases of protein isolation and extraction.
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Christensen, Mikkel Killingmoe & Lund, Reidar
(2019).
Karakterisering av nanostrukturen og vannpermeabiliteten til selvassosierende systemer ved bruk av spredningsteknikker.
Universitetet i Oslo.
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.
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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.
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.
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Bjørnestad, Victoria Ariel & Lund, Reidar
(2018).
Liposomes as a model system for the
study of surface active peptides.
Universitetet i Oslo.
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Med den økende forekomsten av multiresistente patogene organismer er det et stort behov for alternativer til de konvensjonelle antimikrobielle medisinene som finnes på markedet i dag. Antimikrobielle peptider (AMPer) er lovende som utgangspunkt for å utvikle fremtidens antibiotika, men mer kunnskap om virkningsmekanismen deres er nødvendig for at dette skal være mulig. Det er kjent at peptidene interagerer med plasmamembranen til mikrobene og at denne interaksjonen er nødvendig for den antimikrobielle aktiviteten. For å undersøke disse lipidspesifikke interaksjonene til AMP ville vi bruke liposomer, sfæriske fosfolipidbilag, som etterlikner membranene til bakterier og pattedyr. Strukturelle endringer i bilaget ved tilsetning av peptid kan da karakteriseres. Lavvinkel røntgen/nøytronspredning (SAXS/SANS) er optimale teknikker for å undersøke endringene på nanoskala. Det er derimot funnet at liposomer alene feller ut i løsninger med AMPer, som gjør at det ikke er mulig å se den mikroskopiske virkningsmekanismen med disse teknikkene. Det trengtes derfor en metode for å stabilisere liposomene mot aggregering som fortsatt tillot peptidene tilgang til å påvirke membranen. I denne oppgaven har to typer polyetylenoksidderivater blitt testet for deres potensial for å stabilisere liposomer for AMP-indusert aggregering. Begge de modifiserte liposomsystemene sin kinetiske stabilitet, struktur og interaksjon ble testet, med og uten tilsatt AMP. I tillegg ble en kjent flokkulant, polyetylenimin (PEI) testet på systemet for sammenlikning med peptidet. Det ene systemet besto av å tilsette n-alkyl-polyetylenoksid (Cn-PEO) etter liposomene var blitt laget. For det andre systemet ble polyetylenoksidmodifiserte fosfolipider ("PEGylerte" lipider) inkludert i bilaget under preparasjonen. Begge metodene stabiliserte liposomene gjennom sterisk repulsjon. Selv om tilsetning av n-alkyl-polyetylenoksid gjør systemet mer fleksibelt når det kommer til tilberedning, ble det vist at Cn-PEO påvirker membranstrukturen til liposomene i stor grad. Ved 37 grader celsius løser Cn-PEO delvis opp bilager og lager blandede miceller med fosfolipidene, og de vekselvirker også med peptidene. De mange uønskede interaksjonene gir resultater som er vanskelige å analysere. De PEGylerte lipidene stabiliserte derimot liposomene uten å introdusere noen av disse uønskede effektene i systemet. Polymerne på overflaten påvirket heller ikke peptidet sin tilgang til membranen. For å kunne kvantitativt analysere data fra lavvinkelspredningen, ble analytiske spredningsmodeller utviklet både for liposomsystemet og for å beskrive innsetning av peptid i denne systemet. Disse modellene kunne beskrive de eksperimentelle dataene fullstendig. Et av de mer populære påstandene for AMPer er at de gjør membranen mer permeabel for vann og kan dermed utligne protongradienter. Det valgte modellsystemet ble derfor testet for tiden det tok for vann å utveksle over membranen ved å bruke SANS for å se om metoden kunne brukes til å studere effekten AMP har på vanntransporten. Fordelen SANS har over andre metoder som måler diffusjonen av vann er at man kan samtidig se endringer i struktur. Fullstendig utveksling av vann skjedde derimot raskere enn det som kunne måles for alle liposomene som ble testet. Dette skjedde uten tilsats av peptid som viser at lipid membraner er fullstendig permeabel for vann på eksperimentelle tidsskalaer.
