Structural changes in vesicle membranes and mixed micelles of various lipid compositions after binding of different bile salts

Binding equilibria of common bile salts (BS) and different mixtures of membrane lipids were correlated with BS-induced structural changes of large unilamellar vesicles, with transition of vesicles to mixed micelles (MM), and with successive transformations of MM. At very low BS concentrations, in the outer vesicle monolayer definite BS/lipid aggregates are formed, the size and BS binding strength of which depend on the BS and lipid species involved. At increasing BS concentrations, binding to the membranes is hampered, and above a critical BS content, membrane stress due to asymmetric BS binding leads to formation of transient membrane holes, as shown by inulin release from the vesicles. Independent of the BS and lipid species, membrane solubilization starts at a ratio r = 0.3 of bound BS/lipid. Increasing phosphatidylserine, phosphatidylethanolamine, and cholesterol contents stabilize the lecithin membrane against BS to different degrees and in different ways, whereas the destabilization by sphingomyelin is probably due to the enhancement of the membrane gel-liquid transition temperature. Conjugation of the BS with glycine or taurine has a modulating effect on membrane hole formation, rather than on lipid solubilization. Diphenylhexatriene fluorescence anisotropy indicates a BS-induced drop of the internal membrane order and its restoration during membrane solubilization. At higher concentrations ursodeoxycholate induces additional condensation, whereas the other BS cause internal disorder in the MM. Above ratios r of approximately 8:1, we found a release of BS from these MM and suggest a rodlike structure for them. The results were discussed with respect to BS/membrane interactions during lipid excretion from the liver cell.