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 membrane. 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 determine if magainins perturb the lipid sufficiently to permeabilize the bilayer, their effect on the motion of fatty acid and lipid spin labels in phosphatidylcholine/phosphatidylglycerol (PC/PG) lipid vesicles was determined. Their effect was compared to two synthetic peptides, 18L and Ac-18A-NH(2), designed to mimic the naturally occurring classes of lytic (class L) and apolipoprotein (class A) amphipathic helices, respectively. We show that although magainins and 18L both had significant effects on lipid chain order, much greater than Ac-18A-NH(2), there was no correlation between these effects and the relative ability of these three peptide classes to permeabilize PC/PG vesicles in the order magainins=Ac-18A-NH(2) >> 18L. This suggests that the perturbing effects of magainins on lipid chain order at permeabilizing concentrations are not directly responsible for the increased leakage of vesicle contents. The greater ability of the magainins to permeabilize 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-NH(2) relative to 18L to permeabilize PC/PG vesicles despite its lack of disordering effect must be due to its ability to cause membrane fragmentation. Effects of these peptides on other lipids indicated that the mechanism by which they permeabilize lipid bilayers depends both on the peptide and on the lipid composition of the vesicles.
Boggs
J M
JM
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Jo
E
E
Polozov
I V
IV
Epand
R F
RF
Anantharamaiah
G M
GM
Blazyk
J
J
Epand
R M
RM
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005227:Fatty Acids / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D010539:Permeability; D013113:Spin Labels; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides; D005227:Fatty Acids; D008051:Lipid Bilayers; D013113:Spin Labels; C101695:alanine(19)-magainin 2 amide; C067773:magainin A