Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides

Permeation of the cell membrane leading to cell death is a mechanism used b y a large number of membrane-lytic peptides. Some are linear, mostly helica l, and others contain one or more disulfide bonds forming beta-sheet or bot h beta-sheet and alpha-helix structures. They are all soluble in solution b ut when they reach the target membrane, conformational changes occur which let them associate with and lyse the membrane. Some lytic peptides are not cell-selective and lyse different microorganisms and normal mammalian cells , while others are specific to either type of cells. Despite extensive stud ies, the mode of action of membrane-lytic peptides is not fully understood and the basis for their selectivity towards specific target cells is not kn own. Many studies have shown that peptide-lipid interactions leading to mem brane permeation play a major role in their activity. Membrane permeation b y amphipathic alpha-helical peptides has been proposed to occur via one of two general mechanisms: (i) transmembrane pore formation via a 'barrel-stav e' mechanism; and (ii) membrane destruction/solubilization via a 'carpet' m echanism. This review, which is focused on the different stages of membrane permeation induced by representatives of amphipathic alpha-helical antimic robial and cell non-selective lytic peptides distinguishes between the 'car pet' mechanism, which holds for antimicrobial peptides versus the 'barrel-s tave' mechanism, which holds for cell non-selective lytic peptides. (C) 199 9 Elsevier Science B.V. All rights reserved.