Computer Simulation of the Solubilization of Liposomes by Bile Salts

The solubilization of a small unilamellar vesicle by bile salts is studied using Monte Carlo and Langevin dynamics simulation with an implicit solvent. By using coarse-grained models of dipalmitoylphosphatidylcholine and sodium cholate, it has been shown that the mechanism of transition from vesicle to mixed-micelle consists of the following stages: (a) separation of the bile salts from the solution phase and adsorption on the vesicle membrane, (b) enhanced pore formation with increasing bile salt concentration in the membrane, (c) detachment of worm-like mixed micelles from the pores, and (d) decay of the worm-like mixed micelles into smaller mixed micelles which have a reduced ratio of lipid to cholate molecules.