Rationalizing the membrane interactions of cationic amphipathic antimicrobial peptides by their molecular shape

Biophysical and structural studies of cationic amphipathic antimicrobial peptides have revealed new mechanistic details concerning their membrane interactions. In interfacial environments the peptides adopt amphipathic conformations and the resulting distribution of polar, charged and hydrophobic residues allows them to partition into the bilayer interface. For several helical peptides it was found that their long axis is oriented parallel to the membrane surface, an arrangement which results in considerable perturbations in the packing of the lipid bilayer. Within the molecular shape concept the peptides act as wedge-like structures which impose positive curvature strain on the membrane. As a consequence a wide variety of morphologies are observed of peptide–lipid mixtures which strongly depend on the detailed peptide sequence, the membrane lipid composition, buffer, temperature and other environmental parameters. Therefore, the peptide–lipid systems are best described by phase diagrams, similar to the ones of detergent–lipid mixtures, encompassing on the one extreme regions where the peptide stabilizes the bilayer and on the other extreme regions where membrane lysis occurs. The effects of peptide sequence, membrane penetration depth, lipid composition and membrane surface charge density on membrane-association, -morphology and the resulting phase boundaries are discussed.