AMPHIPATHIC PEPTIDE AFFECTS THE LATERAL DOMAIN ORGANIZATION OF LIPID BILAYERS

Using lipid-specific fluorescent probes, we studied the effects of amp hipathic helical, membrane active peptides of the A- and L-type on mem brane domain organization. In zwitterionic binary systems composed of mixtures of phosphatidylcholine and phosphatidylethanolamine, both typ es of peptides associated with the fluid phase. While binding with hig h affinity to fluid membranes, peptides were unable to penetrate into the lipid membrane in the gel state. If trapped kinetically by cooling from the fluid phase, peptides dissociated from the gel membrane on t he time scale of several hours. While the geometrical shape of the cr- helical peptides determines their interactions with membranes with non -bilayer phase propensity, the shape complementarity mechanism by itse lf is unable to induce lateral phase separation in a fluid membrane. C harge-charge interactions are capable of inducing lateral domain forma tion in fluid membranes. Both peptides had affinity for anionic lipids which resulted in about 30% enrichment of acidic lipids within severa l nanometers of the peptide's tryptophan, but there was no long-range order in peptide-induced lipid demixing. Peptide insertion in fluid ac idic membranes was accompanied by only a small increase in bilayer sur face and a decrease in polarity in the membrane core. Peptide-lipid ch arge-charge interactions were also capable of modulating existing doma in composition in the course oi the main phase transition in mixtures of anionic phosphatidylglycerol with zwitterionic phosphatidylcholine. (C) 1997 Elsevier Science B.V.