Interaction of a Short Antimicrobial Peptide on Charged Lipid Bilayer: A Case Study on Aurein 1.2 Peptide

Aurein 1.2 is a short but potent α-helical membrane-active antimicrobial peptide that has shown inhibition on a broad spectrum of bacteria and anti-cancer cell activity. With well-defined helicity, amphipathicity, and cationic charges, it readily binds to membranes and causes membrane change and disruption. This study provides details on how Aurein 1.2 interacts with charged lipid membranes by using neutron membrane diffraction (NMD) and neutron spin echo (NSE) spectroscopy on complex peptide-membrane systems. NMD provides higher resolution lipid bilayer structures than solution scattering. NMD revealed the peptide is mostly associated in the lipid headgroup region. Even at moderately high concentrations (e.g., peptide:lipid ratio of 1:30), aurein is located at the acyl chain-headgroup region without deep penetration into the hydrophobic acyl chain. However, it does reduce the elasticity of the membrane at that concentration, which was corroborated by the NSE results. Furthermore, NSE shows that aurein first softens the membrane, like other α-helical peptides at low concentration, but then makes the membrane much more rigid, even without membrane pore formation. The evidence shows that the action of aurein is quite strong for modifying charged lipid distribution without the need to form membrane pores or disintegrate membranes.