摘要：SummaryVery few drugs in clinical practice feature the chemical diversity, narrow therapeutic window, unique route of administration, and reversible cognitive effects of volatile anesthetics. The correlation between their hydrophobicity and their potency and the increasing amount of evidence suggesting that anesthetics exert their action on transmembrane proteins, justifies the investigation of their effects on phospholipid bilayers at the molecular level, given the strong functional and structural link between transmembrane proteins and the surrounding lipid matrix. Molecular dynamics simulations of a model lipid bilayer in the presence of ethylene, desflurane, methoxyflurane, and the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (also called F6 or 2N) at different concentrations highlight the structural consequences of VA partitioning in the lipid phase, with a decrease of lipid order and bilayer thickness, an increase in overall lipid lateral mobility and area-per-lipid, and a marked reduction in the mechanical stiffness of the membrane, that strongly correlates with the compounds' hydrophobicity.Graphical abstractDisplay OmittedHighlights•Molecular simulations of lipid bilayer interaction with volatile anesthetics•Comparison of volatile anesthetics' and nonimmobilizers' effects on lipid bilayers•Ligand-dependent partitioning of the compounds in the lipid phase•Effects on bilayer thickness, stiffness, and lipid order upon ligand partitioningMolecular physiology; Membrane architecture; Cell biology; Structural biology
