Gallstones are essentially large crystals of cholesterol found in bile (Gr. chole, bile; stereos, solid), an important biological fluid. Bile is secreted by the liver and contains bile salts, which are needed for digestion of lipids, plus the phospholipid lecithin, a primary constituent of cell membranes. The gallbladder stores bile between meals, and Gallstones result when cholesterol precipitates from bile during this storage period.
Cholesterol is insoluble in water, and precipitation from bile at first appears unavoidable. However, bile salts and lecithin are biological surfactants (i.e., they are amphiphilic) that self-assemble in bile and give rise to interesting microstructures that serve as cholesterol transport vehicles. For example, lecithin vesicles enhance the solubility of cholesterol in bile nearly one million fold. Such vesicles are thermodynamically metastable so that cholesterol crystals will ultimately prevail at equilibrium. Attainment of equilibrium is typically slow enough that cholesterol passes through the gallbladder without consequence, but diseased individuals are not so fortunate. Kinetic factors, presumably proteins, influence the rate at which vesicles yield crystals, and the question of who develops gallstones is a matter of chemical kinetics, not thermodynamics.
Our gallstone research aims at prevention of gallstones in humans by determining the mechanisms by which various proteins influence the rate of gallstone formation. We recently developed (the first) analytical technique that detects cholesterol nucleation in bile. We are currently using this technique, a fluorescence assay, to study cholesterol nucleation kinetics. Our research deals with thermodynamic and kinetic aspects of the various microstructural transitions in bile and is certainly a molecular level approach. However, we collaborate with clinicians at the University of Washington School of Medicine, and our work has significant practical implications.
NEW! Our work is now featured on-line by several health magazines.