Interdigitation and vesicle-to-micelle transformation induced by a local anesthetic tetracaine in phospholipids bilayers

The phase transitions of distearoyl- (DSPC), dipalmitoyl- (DPPC) and dimyristoyl-phosphatidylcholine (DMPC) bilayer membranes were observed by means of differential scanning calorimetry as a function of the concentration of a local anesthetic tetracaine hydrochloride (TC·HCl). The depression of both temperatures of the main- and pre-transition, which is accompanied by a decrease in enthalpy changes for both transitions, was observed initially by the addition of TC·HCl. Bilayer interdigitation, which is accompanied by an increase in enthalpy change for the main transition from the interdigitated gel phase to the liquid crystalline phase, was followed by disappearance of the pretransition. The TC·HCl concentration necessary for the bilayer interdigitation was found to be 10, 21 and 6 mmol kg−1 for DSPC, DPPC and DMPC bilayers, respectively, which was not consistent with the order of acyl-chain length of lipids. Biphasic interactions for the interdigitation, that is, repulsive interaction between polar head groups and van der Waals attractive interaction between hydrophobic chains of lipids, were discussed. On the other hand, vesicle-to-micelle transformation, which is accompanied by a cooperative decrease in enthalpy change for the main transition, was observed at higher concentration of TC·HCl and was confirmed by the vesicle size determined by the dynamic light scattering. The longer the acyl-chain length of lipids, the higher the TC·HCl concentration necessary for the vesicle-to-micelle transformation.