ROLE OF LIPIDS IN THE PERMEABILIZATION OF MEMBRANES BY CLASS-L AMPHIPATHIC HELICAL PEPTIDES

We studied the mechanism of membrane permeabilization by the 18L model peptide (GIKKFLGSIWKFIKAFVG), which features the consensus class L se quence averaged from the number of naturally occurring lytic peptides. Two aspects of membrane lipid composition significantly affected pept ide-membrane interactions: the presence of acidic Lipids and, in zwitt erionic membranes, and the presence of nonbilayer forming lipids. In z witterionic membranes, 18L peptide destabilizes the membrane, leading to a transient formation of large defects in the membrane which result generally in contents leakage, but in the presence of bilayer-bilayer contact can alternatively lead to vesicle fusion. In membranes contai ning acidic lipids (DOPC:DOPG, DOPG), 18L caused leakage but not fusio n, probably due to mutual repulsion of acidic vesicles. While the exte nt of contents leakage was approximately the same as for zwitterionic membranes, the kinetics of leakage could be resolved only by using sto pped-flow, leakage being essentially complete within the first minute. Previously, we reported that apolipoprotein (class A) and lytic (clas s L) peptide analogs have opposing effects on some properties of biolo gical membranes. This reciprocal effect of 18L and Ac-18A-NH2, class A model peptide, is restricted to membranes with a high propensity for nonbilayer phase formation (DOPE, Me-DOPE, DOPC:DOPE, DOPC:Me-DOPE). T he decrease in the content of nonbilayer phase forming lipid or the ad dition of acidic lipids reduces or eliminates the reciprocal effects. This suggests the importance of nonbilayer phase propensity for certai n functions of biological membranes.