title: Sigmoidal concentration dependence of antimicrobial peptide activities: a case study on alamethicin.
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.
authors.affiliation: Department of Physics, National Central University, Chung-Li, Taiwan 32054.
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Chen
authors.forename: Ming-Tao
authors.initials: MT
authors.lastname: Lee
authors.forename: Huey W
authors.initials: HW
authors.lastname: Huang
mesh_terms: D000408:Alamethicin / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008823:Micelles; D010455:Peptides / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D008823:Micelles; D010455:Peptides; D000408:Alamethicin