Mechanism of supported membrane disruption by antimicrobial peptide protegrin-1.
While pore formation has been suggested as an important step in the membrane disruption process induced by antimicrobial peptides, membrane pore formation has never been directly visualized. We report on the dynamics of membrane disruption by antimicrobial peptide protegrin-1 (PG-1) on dimyristoyl-sn-glycero-phosphocholine-supported bilayer patches obtained via atomic force microscopy. The action of PG-1 is found to be concentration-dependent. At low PG-1 concentrations (1 < [PG-1] < 4 microg/mL), the peptide destabilizes the edge of the membrane to form fingerlike structures. At higher concentrations, PG-1 induces the formation of a sievelike nanoporous structure in the membrane. The highest degree of disruption is attained at concentrations >or=20 microg/mL, at which PG-1 disrupts the entire membrane, transforming it into stripelike structures with a well-defined and uniform stripe width. This first direct visualization of these membrane structural transformations helps elucidate the PG-1-induced membrane disruption mechanism.
Lam
Kin Lok H
KL
Department of Physics, The Institute for Biophysical Dynamics, and The James Franck Institute, The University of Chicago, Illinois 60637, USA.
Ishitsuka
Yuji
Y
Cheng
Yishan
Y
Chien
Karen
K
Waring
Alan J
AJ
Lehrer
Robert I
RI
Lee
Ka Yee C
KY
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004134:Dimyristoylphosphatidylcholine; D008051:Lipid Bilayers / Q000378:metabolism*; D008954:Models, Biological; D016062:Porosity; D011506:Proteins / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D011506:Proteins; C094880:protegrin-1; D004134:Dimyristoylphosphatidylcholine