title: The electrical response of bilayers to the bee venom toxin melittin: evidence for transient bilayer permeabilization.
abstract: Melittin is a 26-residue bee venom peptide that folds into amphipathic α-helix and causes membrane permeabilization via a mechanism that is still disputed. While an equilibrium transmembrane pore model has been a central part of the mechanistic dialogue for decades, there is growing evidence that a transmembrane pore is not required for melittin's activity. In part, the controversy is due to limited experimental tools to probe the bilayer's response to melittin. Electrochemical impedance spectroscopy (EIS) is a technique that can reveal details of molecular mechanism of peptide activity, as it yields direct, real-time measurements of membrane resistance and capacitance of supported bilayers. In this work, EIS was used in conjunction with vesicle leakage studies to characterize the response of bilayers of different lipid compositions to melittin. Experiments were carried out at low peptide to lipid ratios between 1:5000 and 1:100. The results directly demonstrate that the response of the bilayer to melittin at these concentrations cannot be explained by an equilibrium transmembrane pore model.
authors: Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors: Gregory
authors: G
authors: Wiedman
authors: Katherine
authors: K
authors: Herman
authors: Peter
authors: P
authors: Searson
authors: William C
authors: WC
authors: Wimley
authors: Kalina
authors: K
authors: Hristova
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000737:chemistry*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D058266:Dielectric Spectroscopy; D055590:Electromagnetic Phenomena; D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry* / Q000494:pharmacology; D008563:Membrane Lipids / Q000737:chemistry; D010539:Permeability / Q000187:drug effects; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D013997:Time Factors; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D001514:Bee Venoms; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D053835:Unilamellar Liposomes; D008555:Melitten; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
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