Induction of non-lamellar lipid phases by antimicrobial peptides: a potential link to mode of action

Antimicrobial peptides are naturally produced by numerous organisms including insects, plants and mammals. Their non-specific mode of action is thought to involve the transient perturbation of bacterial membranes but the molecular mechanism underlying the rearrangement of the lipid molecules to explain the formation of pores and micelles is still poorly understood. Biological membranes mostly adopt planar lipid bilayers; however, antimicrobial peptides have been shown to induce non-lamellar lipid phases which may be intimately linked to their proposed mechanisms of action. This paper reviews antimicrobial peptides that alter lipid phase behavior in three ways: peptides that induce positive membrane curvature, peptides that induce negative membrane curvature and peptides that induce cubic lipid phases. Such structures can coexist with the bilayer structure, thus giving rise to lipid polymorphism induced upon addition of antimicrobial peptides. The discussion addresses the implications of induced lipid phases for the mode of action of various antimicrobial peptides.