Sigmoidal concentration dependence of antimicrobial peptide activities: a case study on alamethicin

Biophys J. 2002 Feb;82(2):908-14. doi: 10.1016/S0006-3495(02)75452-0.

Abstract

The transition of the state of alamethicin from its inactive state to its active state of pore formation was measured as a function of the peptide concentration in three different membrane conditions. In each case the fraction of the alamethicin molecules occupying the active state, phi, showed a sigmoidal concentration dependence that is typical of the activities of antimicrobial peptides. Such a concentration dependence is often interpreted as due to peptide aggregation. However, we will show that a simple effect of aggregation cannot explain the data. We will introduce a model based on the elasticity of membrane, taking into consideration the membrane-thinning effect due to protein inclusion. The elastic energy of membrane provides an additional driving force for aggregation. The model produces a relation that not only predicts the correct concentration dependence but also explains qualitatively how the dependence changes with membrane conditions. The result shows that the membrane-mediated interactions between monomers and aggregates are essential for the strong cooperativity shown in pore formation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alamethicin / chemistry*
  • Alamethicin / pharmacology*
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Circular Dichroism
  • Dose-Response Relationship, Drug
  • Kinetics
  • Micelles
  • Peptides / chemistry

Substances

  • Anti-Bacterial Agents
  • Micelles
  • Peptides
  • Alamethicin