Liquid crystals and cholesterol nucleation during equilibration in supersaturated bile analogs

In recent work, apparent liquid crystal agglomeration to form typical solid cholesterol microcrystals was frequently observed photomicrographically in bile samples from prairie dogs fed a cholesterol-enriched diet, prior to solid crystal formation. We therefore have conducted a systematic study of time-course lipid compositional changes in the mesophase and micellar phase constituents of bile analog solutions while undergoing cholesterol nucleation during equilibration. On the basis of these studies, we conclude that the nucleation process for microcrystal formation most likely occurs within the mesophase component which is only the first of a two-step transition in a sequential series of physical ordering processes. We deduce that mesophase formation must have a lower kinetic energy requirement and that the second step (microcrystal formation) must be rate limiting. In keeping with theoretical considerations, structural evidence for increased hydration is demonstrable near the point of complete equilibration when the mesophase is dissolving.