Interaction of cationic antimicrobial peptides with model membranes

A series of natural and synthetic cationic antimicrobial peptides from vari ous structural classes, including a-helical, beta -sheet, extended, and cyc lic, were examined for their ability to interact with model membranes, asse ssing penetration of phospholipid monolayers and induction of lipid flip-fl op, membrane leakiness, and peptide translocation across the bilayer of lar ge unilamellar liposomes, at a range of peptide/lipid ratios. All peptides were able to penetrate into monolayers made with negatively charged phospho lipids, but only two interacted weakly with neutral lipids. Peptide-mediate d lipid flipflop generally occurred at peptide concentrations that were 3- to 5-fold lower than those causing leakage of calcein across the membrane, regardless of peptide structure. With the exception of two alpha -helical p eptides V681(n) and V25(p), the extent of peptide-induced calcein release f rom large unilamellar liposomes was generally low at peptide/lipid molar ra tios below 1:50. Peptide translocation across bilayers was found to be high er for the beta -sheet peptide polyphemusin, intermediate for alpha -helica l peptides, and low for extended peptides. Overall, whereas all studied cat ionic antimicrobial peptides interacted with membranes, they were quite het erogeneous in their impact on these membranes.