Effect of dibucaine hydrochloride on raft-like lipid domains in model membrane systems

Abstract

To clarify the biophysical and/or physicochemical mechanism of anaesthesia, we investigated the influence of dibucaine hydrochloride (DC·HCl), a local anaesthetic, on raft-like domains in ternary liposomes composed of dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol). The large DOPC/DPPC/Chol liposome is directly observable by optical microscopy and is known to be laterally separated into a liquid-ordered (Lo) phase (raft-like domain) and liquid-disordered (Ld) phase under certain conditions. Hence, it is useful for the study of lipid raft domains as a simple model system of cell membranes. We observed ternary liposomes with three concentrations (0, 0.05 and 0.2 mM) of DC·HCl at various temperatures and calculated the angle-averaged two-dimensional autocorrelation functions to confirm the change in miscibility transition temperature (T c) of ternary liposomes. Furthermore, we calculated the circularity of the Lo domain to confirm the change in line tension of the Lo/Ld phase boundary. The results indicated that the insertion of DC molecules into lipid bilayers induces reduction in T c of the ternary liposome, accompanied by reduction in line tension of the phase boundary. This suggests that the DC·HCl molecules may disturb ion channel functions by affecting the lipid bilayers surrounding the ion channels.