Revisiting lipid – general anesthetic interactions (I): Thinned domain formation in supported planar bilayers induced by halothane and ethanol

A long-standing question in anesthesia is that of the molecular mechanism. Do anesthetics target proteins or change membrane properties or both? We used temperature-dependent magnetic A/C mode atomic force microscopy (AFM) to study interaction of the volatile anesthetics halothane and ethanol with model membranes made from supported planar bilayers (SPBs) of 1,2-dioleoyl-sn-3-glycero-3-phosphocholine (DOPC), dioleoyltrimethylammonium propane (DOTAP), or 1,2-dipalmitoyl-sn-3-glycero-3-phosphocholine (DPPC). We found that the incorporation of halothane or ethanol induces structural changes in the bilayer. These compounds cause thickness reduction in L α bilayers (either globally or in domains) and the formation of domains with reduced thickness in L β phase bilayers. We propose that an anesthetic-induced increased area per lipid drives local chain disorder, thus promoting local phase change. The characteristics of SPBs with halothane or ethanol incorporated were compared with characteristics of the L α and L β phases of anesthetic-free SPBs.Key words: atomic force microscopy, anesthesia, lipid bilayer domains, phase transition