Effect of magainin, class L, and class A amphipathic peptides on fatty acid spin labels in lipid bilayers

Magainins and other antimicrobial peptides increase ion flux across the mem brane. They may do this by forming some type of pore or by perturbing lipid organization due to peptide lying on the bilayer surface. In order to dete rmine if magainins perturb the lipid sufficiently to permeabilize the bilay er, their effect on the motion of fatty acid and lipid spin labels in phosp hatidylcholine/phosphatidylglycerol (PC/PG) lipid vesicles was determined. Their effect was compared to two synthetic peptides, 18L and Ac-18A-NH2, de signed to mimic the naturally occurring classes of lytic (class L) and apol ipoprotein (class A) amphipathic helices, respectively. We show that althou gh magainins and 18L both had significant effects on lipid chain order, muc h greater than Ac-18A-NH2, there was no correlation between these effects a nd the relative ability of these three peptide classes to permeabilize PC/P G vesicles in the order magainins =Ac-18A-NH(2)much greater than 18L. This suggests that the perturbing effects of magainins on lipid chain order at p ermeabilizing concentrations are not directly responsible for the increased leakage of vesicle contents. The greater ability of the magainins to perme abilize PC/PG vesicles relative to 18L is thus more likely due to formation of some type of pore by magainins. The greater ability of Ac-18A-NH2 relat ive to 18L to permeabilize PC/PG vesicles despite its lack of disordering e ffect must be due to its ability to cause membrane fragmentation. Effects o f these peptides on other lipids indicated that the mechanism by which they permeabilize lipid bilayers depends both on the peptide and on the lipid c omposition of the vesicles. (C) 2001 Elsevier Science B.V. All rights reser ved.