title: Real-time measurement of membrane conformational states induced by antimicrobial peptides: balance between recovery and lysis.
abstract: The disruption of membranes by antimicrobial peptides is a multi-state process involving significant structural changes in the phospholipid bilayer. However, direct measurement of these membrane structural changes is lacking. We used a combination of dual polarisation interferometry (DPI), surface plasmon resonance spectroscopy (SPR) and atomic force microscopy (AFM) to measure the real-time changes in membrane structure through the measurement of birefringence during the binding of magainin 2 (Mag2) and a highly potent analogue in which Ser(8), Gly(13) and Gly(18) has been replaced with alanine (Mag-A). We show that the membrane bilayer undergoes a series of structural changes upon peptide binding before a critical threshold concentration is reached which triggers a significant membrane disturbance. We also propose a detailed model for antimicrobial peptide action as a function of the degree of bilayer disruption to provide an unprecedented in-depth understanding of the membrane lysis in terms of the interconversion of different membrane conformational states in which there is a balance between recovery and lysis.
authors: 1] Department of Biochemistry & Molecular Biology, Monash University, Clayton Vic 3800, Australia [2].
authors: Kristopher
authors: K
authors: Hall
authors: 1] Department of Biochemistry & Molecular Biology, Monash University, Clayton Vic 3800, Australia [2].
authors: Tzong-Hsien
authors: TH
authors: Lee
authors: 1] School of Molecular Sciences, La Trobe University, Bundoora Vic 3083, Australia [2].
authors: Adam I
authors: AI
authors: Mechler
authors: Farfield, Biolin Scientific 3000, Manchester Business Park, Aviator Way, Manchester, M22 5TG, United Kingdom.
authors: Marcus J
authors: MJ
authors: Swann
authors: Department of Biochemistry & Molecular Biology, Monash University, Clayton Vic 3800, Australia.
authors: Marie-Isabel
authors: MI
authors: Aguilar
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008968:Molecular Conformation / Q000187:drug effects*; D020349:Surface Plasmon Resonance
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers