Short 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 understood 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 combine experimental time-resolved small angle X-ray scattering with a theoretical diffusional model based on molecular dynamics simulation data 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 work reveals 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, MD data reveal the formation of transient, ion-conducting water channels, associated with the peptide-enhanced lipid scrambling dynamics, which explain the observed ion transport quantitatively better than hypothetic stable pores.
Publication
Oct, 28th 2025:
Funding
The Research Council of Norway and Hylleraas Centre for Quantum Molecular Sciences (262695).