Effect of Cholic Acid Salt and Its Mixed Micelles on the Morphology of Giant Unilamellar Vesicles (GUV)

Bile salts, present in the gastrointestinal tract as biosurfactants, play a crucial role in emulsifying and solubilizing fat-soluble nutrients and drugs, thereby facilitating their absorption. However, the cellular permeation of bile acid-mixed micelles solubilized with lipophilic substances remains inadequately explored. To comprehend the cell permeation behavior of bile salts and their mixed micelles, giant unilamellar vesicles (GUVs) were employed as a cell-mimetic system, prepared with dioleylphosphatidylcholine (DOPC). Confocal laser scanning microscopy, utilizing fluorescent dyes doped in the lipid membrane and solubilized substances, was employed to observe morphological changes in GUVs subsequent to the application of sodium cholate (NaC) alone and NaC-mixed micelles solubilized with lipophilic components. In the case of NaC alone, below the critical micelle concentration (CMC), the monomer interacts with the lipid membrane of the GUV, inducing endocytic morphological changes that result in the formation of small vesicles containing the bulk liquid inside the GUV. Conversely, when both monomers and micelles interacted with the lipid membrane beyond the CMC, lipid aggregates such as buds and threads protruded outward from the GUV. Contrastingly, upon application of three types of NaC mixed micelles-NaC-P solubilized with Palmitoyloleoylphosphocholine (POPC), NaC-P-F solubilized with oleic acid (OA) and monoolein (MO), and NaC-P-P solubilized with perylene, a liposoluble dye-to the GUV, the lipid membranes formed aggregates or vesicles and migrated into the interior of the GUV. In the case of NaC-P and NaC-P-P, the coexistence of drawn lipid aggregates and solubilized substances was scarcely observed. In contrast, for NaC-P-F, the coexistence of solubilized substances was observed in both lipid aggregates and small vesicles that migrated into the GUV. It is suggested that the partitioning of the solubilized substance from the mixed micelles adsorbed on the GUV to the lipid bilayer is implicated in the permeation of the solubilized substance through the cell membrane.