Structural dimorphism of bile salt/lecithin mixed micelles. A possible regulatory mechanism for cholesterol solubility in bile? X-ray structure analysis.

Abstract

The three-dimensional structure of bile salt/lecithin mixed micelles in 0.15 M saline was derived from X-ray small-angle scattering measurements under various conditions. Two essentially different types of micelles were detected. At bile salt:lecithin molar ratios lower than approximately 2:1, lamellar particles similar to a lecithin bilayer arrangement were found. The thickness of the bilayer is 5.1 nm for mixed micelles having a molar ratio of 1:1. The lateral dimensions of the micelle were found strongly dependent upon molar ratio, increasing as lecithin content increases. In addition, it appeared that under certain incompletely defined conditions vesicular particles having diameters in the region of more than 100 nm occur. A molecular model of this type of micelle has been derived by means of a thorough interpretation of the electron density distribution across the plane of the bilayer. This model is generally consistent with the "mixed-disk" model of Mazer et al. [Mazer, N. A., Kwasnick, R. F., Carey, M. C., & Benedek, G. B. (1977) Micellization, Solubilization, Microemulsions, Proc. Int. Symp. 1, 383-402] and thus differs from that proposed by Small [Small, D. M. (1967) Gastroenterology 52,607-610] and Dervichian [Dervichian, D. G. (1968) Adv. Chem. Ser. No. 84, 78-87]. At molar ratios exceeding 2:1, a different type of micelle structure was found. This is a highly isometrical particle of globular shape, probably having a centrosymmetric arrangement of the molecular constituents. At a 3:1 bile salt:lecithin molar ratio, the mean physiological ratio for human gallbladder bile, the diameter of this micelle is 6.2 nm. Provided that other bile constituents have no significant influence on the structure, it may reasonably be expected that native gallbladder bile contains micelles of this latter type. The prevalent balance between the two micellar forms may thus regulate the capacity of bile to transport cholesterol.