Characterization of the self-assembly and size dependent structural properties of dietary mixed micelles by molecular dynamics simulations

Abstract

The bile salts and phospholipids are secreted by the gallbladder to form dietary mixed micelles in which the solvation of poorly absorbed lipophilic drugs and nutraceuticals take place. A comprehensive understanding of the micellization and structure of the mixed micelles are crucial to design effective delivery systems for such substances. In this study, the evolution of the dietary mixed micelle formation under physiologically relevant concentrations and the dependence of structural properties on micelle size were investigated through coarse-grained molecular dynamics simulations. The MARTINI force field was used to model cholate and POPC as the representative bile salt and phospholipid, respectively. The micellization behavior was similar under both fasted and fed state concentrations. Total lipids concentration and the micelle size did not affect the internal structure of the micelles. All the micelles were slightly ellipsoidal in shape independent of their size. The extent of deviation from spherical geometry was found to depend on the micellar POPC/cholate ratio. We also found that the surface and core packing density of the micelles increased with micelle size. The former resulted in more perpendicular alignments of cholates with respect to the surface, while the latter resulted in an improved alignment of POPC tails with the radial direction and more uniform core density.

Keywords: Bile salts; Cholate; Dietary mixed micelles; Molecular dynamics simulations; POPC; Self-assembly.