İzmir Institute of Technology, Food Engineering Department, Gulbahce Campus,Urla, Izmir 35430, Turkey.
Biophys Chem. 2019 May;248:16-27. doi: 10.1016/j.bpc.2019.02.001. Epub 2019 Feb 5.
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.
胆汁盐和磷脂由胆囊分泌，形成膳食混合胶束，其中疏水性差的脂溶性药物和营养物质得以溶解。全面了解胶束的胶束化和结构对于设计此类物质的有效递送系统至关重要。在这项研究中，通过粗粒度分子动力学模拟研究了在生理相关浓度下膳食混合胶束形成的演变以及结构特性对胶束大小的依赖性。MARTINI 力场用于分别模拟胆酸盐和 POPC 作为代表性的胆汁盐和磷脂。在禁食和进食状态浓度下，胶束化行为相似。总脂质浓度和胶束大小均不影响胶束的内部结构。所有胶束均呈轻微的椭圆形，与胶束大小无关。偏离球形几何形状的程度取决于胶束中 POPC/胆酸盐的比例。我们还发现，胶束的表面和核心堆积密度随胶束尺寸的增加而增加。前者导致胆酸盐相对于表面的垂直排列更多，而后者导致 POPC 尾部与径向方向的排列更一致，核心密度更均匀。
