Effect of unilamellar vesicle size on ethanol-induced interdigitation in dipalmitoylphosphatidylcholine

Unilamellar liposomes are widely used as model membranes to represent and study the properties of biological membranes and as potential drug delivery systems. It is well established that ethanol and other amphiphiles induce the interdigitated L beta I phase in multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). However, all of the work on this phase has been performed using the hand shaken multilamellar preparations. In the present report, we have studied the induction of interdigitation in a series of unilamellar vesicles prepared by sonication and by extrusion. The methods used to characterize the vesicles were freeze fracture electron microscopy and quasielastic light scattering (QELS). Two fluorescence methods were used to detect interdigitation, the DPH fluorescence quenching method (Nambi, P., Rowe, E.S. and McIntosh, T.J. (1988) Biochemistry 27, 9175-9182) and the pyrene-PC fluorescence method (Komatsu, H. and Rowe, E.S. (1991) Biochemistry 30: 2463-2470). It was found that sonicated vesicles are not stable in the presence of interdigitating concentrations of ethanol; they form higher aggregates at all temperatures examined. The behavior of the extruded vesicles was different from that of the SUV; each size studied was stable in the presence of ethanol, although they exhibited an increase in size. It was shown that extruded vesicles having a 200-nm or greater diameter become interdigitated in the presence of ethanol. The threshold concentration for interdigitation in vesicles is greater than that for MLVs and it decreases with increasing vesicle size, approaching the MLV value for the largest vesicles.