Characterization of lipid solubilization, bicelle formation, and magnetic-alignment induced by saponins

Saponins are a diverse class of plant-derived glycoside natural products. They are amphiphilic surfactants and have been included in food, agriculture, cosmetics, cleaner, and pharmaceutical products as emulsifiers. Interactions between saponins and lipids have been widely studied for these applications. Recently, some binary saponin-phospholipid mixtures have been reported to form disc-shaped colloidal particles, called bicelles or nanodiscs, that align in a magnetic field. These bicelles are potentially useful for a variety of research and biomedical purposes. Here, we used transmittance assays to determine the ability of Quillaja saponins (CQS) to solubilize phospholipids with varied chain lengths and headgroup charges. Then, we used static ³¹P solid-state NMR to construct a temperature-composition diagram of the binary CQS-DMPC system and identify the conditions that allow formation of bicelles and spontaneous alignment in a magnetic field. To improve the homogeneity and reproducibility of bicelle formulations, we investigated lipid solubilization and bicelle formation of DMPC in the presence of seven additional saponin molecules and mixtures. We discovered that the triterpenoid saponins aescin, glycyrrhizic acid, ginsenoside Rb1, and hederacoside C efficiently solubilized DMPC and induced the formation of homogeneous bicelles. The steroid saponin digitonin dissolved DMPC but did not form bicelles. Possible structural determinants of saponin-induced lipid solubilization and bicelle formation are discussed.