Nucleation of cholesterol crystals in native bile

Any substance capable of ultimately forming itself into a solid crystal must undergo an initial step of forming crystal nuclei. The nucleation step in crystallization for all such systems has been a difficult process to describe. Even the definition of what constitutes a "nucleus" remains elusive because one is dealing with a conceptual construct that is found only in the submicroscopic domain and therefore is inaccessible to direct measurement. Based on these considerations, the so-called nucleation time assay can at best only be taken as an empirical parameter. Nucleation (operationally defined) and growth of cholesterol monohydrate crystals in both model and native biles occurs rapidly after aggregation of supersaturated vesicles. Cholesterol made available for crystal growth also originates from the vesicular pathway and not directly from biliary micelles. The exact mechanism(s) governing this linked "precursor-product" relationship remains undefined.