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 Lα bilayers (either globally or in domains) and the formation of domains with reduced thickness in Lβ 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 Lα and Lβ phases of anesthetic-free SPBs.