Pore formation in lipid membranes by alamethicin.
The conformation of the linear peptide antibiotic alamethicin in dipalmitoyl phosphatidylcholine multilayers was investigated in the absence of an electric field by means of infrared attenuated total reflection spectroscopy. Alamethicin was found to be incorporated into the lipid membrane not only in the dry state but also in an aqueous environment. Its molecular conformation, however, changed from a helix when dry to an extended chain when aqueous. The extended chain aggregated to di- and multimers spanning the lipid bilayer. The equilibrium concentration of alamethicin in the surrounding water was 90 nM, which is in the range of concentrations used in black film experiments. The corresponding molar ratio of lipid to peptide was 80:1. Concerning the molecular mechanism of electric field-induced pore formation, one has to conclude that the dipole model proposed by several authors is very unlikely because it is based on the assumption that the major part of alamethicin is adsorbed on the membrane surface, from which small amounts flip into the membrane under the influence of an electric field. An alternative mechanism is proposed, based on a field-induced conformational change of the peptide from the extended state to a helix. This transition is favored by the resulting dipole moment of the alamethicin helix.
D000408:Alamethicin; D000900:Anti-Bacterial Agents; D007473:Ion Channels; D007476:Ionophores; D008051:Lipid Bilayers; D008563:Membrane Lipids; D009038:Motion; D010713:Phosphatidylcholines; D011487:Protein Conformation
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D007476:Ionophores; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D000408:Alamethicin