Effect of Ionic Strength on the Self-Assembly in Mixtures of Phosphatidylcholine and Sodium Cholate

Abstract

The self-assembly of mixtures of the micelle-forming bile salt sodium cholate and the bilayer-forming phosphatidylcholine (PC) depends on the composition of the mixed aggregates, which, in turn, depends on the partitioning of cholate between the mixed aggregate and the aqueous medium. The ionic strength of the aqueous medium is known to reduce the critical micellar concentration of bile salts. Accordingly, increasing the ionic strength of the medium, for any given lipid and cholate concentrations, resulted in a decrease in the concentration of monomeric cholate and in a consequent increase inRe, the [cholate]/[PC] ratio within the mixed aggregate. Changes in the ionic strength are supposed to influence the electric energy of mixed monolayers, the latter favoring formation of strongly curved micelles from the almost flat membranes of the vesicles. We therefore expected the vesicle–micelle phase boundaries, as defined in terms ofReat the onset (ReSAT) and completion (ReSOL) of solubilization, to increase on increasing the salt concentration. The experimental static and dynamic light scattering data presented here show that both phase boundaries are only slightly dependent, if at all, on the ionic strength of the medium. By contrast, the steady-state size of cholate-containing PC vesicles is found to be an increasing function of ionic strength. We explain these results by considering the contributions of electrostatic interactions to the elastic properties of mixed monolayers. Specifically, the phase boundaries are determined by the spontaneous curvature of the monolayers. We show that because the phase boundaries are apparently independent of ionic strength, the influence of ionic strength on the spontaneous curvature is negligible in comparison to the main value determined by the chemical structure of the detergent. By contrast, the electrostatic contribution to the modules of Gaussian curvature, influencing the size of the vesicles, is shown theoretically to become significant at low NaCl concentrations. This explains the dependence of vesicle size on ionic strength.