Title: General Anesthetics Raise the Miscibility Transition Temperature of Model Membranes
Abstract: General anesthetics have been used for over a century, yet their underlying molecular mechanism is still unknown. The potency of a general anesthetic strongly correlates with its affinity for hydrophobic environments, leading several authors to suggest that anesthetics act by altering bulk properties of the cell plasma membrane. In this study, we show that liquid general anesthetics significantly raise the miscibility transition temperature of model membranes. We find that this increase is consistent across a range of n-alcohols and the magnitude of the shift correlates both to concentration and potency of the alcohol. We demonstrate this upward shift in miscibility transition temperature in a diversity of systems with varying lipid ratios and types. This outcome is in the opposite direction of previously published results in plasma membrane-derived vesicles in which general anesthetics cause a depression in transition temperature (Gray et al., BJ, 2013). Our results demonstrate that liquid general anesthetics do indeed alter bulk properties of the membrane and that the potency of general anesthetics correlates with changes in lateral heterogeneity of model membranes. This research was supported by NSF MCB-1402059 and the National Institute of General Medical Sciences of the NIH under award number T32GM008268 to C.C.