Effect of Dibucaine on Phase Behavior of Ternary Liposome

We investigated the effect of Dibucaine hydrochloride (DC$\cdot$HCl), one of the local anesthetics, on phase behavior of ternary liposome composed of dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), and cholesterol (Chol). The large DOPC/DPPC/Chol liposome, that is directly observable by optical microscope, is commonly known to be laterally separated into liquid-ordered (Lo) phase (raft-like domain) and liquid-disordered (Ld) phase under certain conditions and is useful for study of lipid-raft-like domains as a simple model system. In order to confirm the effect of DC$\cdot$HCl on a miscibility transition temperature, $T_{\rm c}$, of the ternary liposome, we observed the liposomes with three concentrations, 0, 0.05, and 0.2~mM, of DC$\cdot$HCl at various temperatures. In addition, we calculated the angle-averaged two-dimensional autocorrelation (2D-AC) functions in order to quantify the phase behavior. The results of these observations and calculations revealed that the DC$\cdot$HCl molecules induce the reduction of $T_{\rm c}$ of the ternary liposome. Furthermore, we calculated the circularity of Lo domain in order to confirm the change in the line tension of the Lo/Ld phase boundary and revealed that the insertion of the DC molecules induces the reduction of line tension. In terms of the critical phenomena, we conclude that the insertion of the DC molecules induces the reduction of the $T_{\rm c}$ of the ternary liposome due to reduction of line tension. This suggests that the DC molecules may disturb function of ion channels via affecting the lipid bilayers which surround ion channels.