Many-body effect of antimicrobial peptides: on the correlation between lipid's spontaneous curvature and pore formation

Biophys J. 2005 Dec;89(6):4006-16. doi: 10.1529/biophysj.105.068080. Epub 2005 Sep 8.

Abstract

Recently we have shown that the free energy for pore formation induced by antimicrobial peptides contains a term representing peptide-peptide interactions mediated by membrane thinning. This many-body effect gives rise to the cooperative concentration dependence of peptide activities. Here we performed oriented circular dichroism and x-ray diffraction experiments to study the lipid dependence of this many-body effect. In particular we studied the correlation between lipid's spontaneous curvature and peptide's threshold concentration for pore formation by adding phosphatidylethanolamine and lysophosphocholine to phosphocholine bilayers. Previously it was argued that this correlation exhibited by magainin and melittin supported the toroidal model for the pores. Here we found similar correlations exhibited by melittin and alamethicin. We found that the main effect of varying the spontaneous curvature of lipid is to change the degree of membrane thinning, which in turn influences the threshold concentration for pore formation. We discuss how to interpret the lipid dependence of membrane thinning.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / chemistry*
  • Lipid Bilayers / chemistry*
  • Melitten / chemistry*
  • Membrane Fluidity*
  • Membrane Lipids / chemistry*
  • Molecular Conformation
  • Porosity
  • Protein Conformation
  • Statistics as Topic

Substances

  • Antimicrobial Cationic Peptides
  • Lipid Bilayers
  • Membrane Lipids
  • Melitten