title: 1-Alkanols and membranes: a story of attraction.
abstract: Although 1-alkanols have long been known to act as penetration enhancers and anesthetics, the mode of operation is not yet understood. In this study, long-time molecular dynamics simulations have been performed to investigate the effect of 1-alkanols of various carbon chain lengths onto the structure and dynamics of dimyristoylphosphatidylcholine bilayers. The simulations were complemented by microcalorimetry, continuous bleaching and film balance experiments. In the simulations, all investigated 1-alkanols assembled inside the lipid bilayer within tens of nanoseconds. Their hydroxyl groups bound preferentially to the lipid carbonyl group and the hydrocarbon chains stretched into the hydrophobic core of the bilayer. Both molecular dynamics simulations and experiments showed that all 1-alkanols drastically affected the bilayer properties. Insertion of long-chain 1-alkanols decreased the area per lipid while increasing the thickness of the bilayer and the order of the lipids. The bilayer elasticity was reduced and the diffusive motion of the lipids within the bilayer plane was suppressed. On the other hand, integration of ethanol into the bilayer enlarged the area per lipid. The bilayer became softer and lipid diffusion was enhanced.
authors.affiliation: Theoretical and Computational Membrane Biology, Center for Bioinformatics, Saarland University, 66041, Saarbrücken, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Griepernau
authors.forename: Simon
authors.initials: S
authors.lastname: Leis
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Schneider
authors.forename: Martin
authors.initials: M
authors.lastname: Sikor
authors.forename: Daniel
authors.initials: D
authors.lastname: Steppich
authors.forename: Rainer A
authors.initials: RA
authors.lastname: Böckmann
mesh_terms: D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D002151:Calorimetry; D002462:Cell Membrane / Q000187:drug effects; D003903:Deuterium; D004058:Diffusion; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004548:Elasticity; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000438:Alcohols; D000777:Anesthetics; D008051:Lipid Bilayers; D003903:Deuterium; D004134:Dimyristoylphosphatidylcholine