Examining the Molecular Mechanism of Antimicrobial Peptides using Neutron and X-ray Scattering Techniques

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