Molecular dynamics simulation of cholesterol nucleation in mixed micelles modelling human bile

摘要

Concentrated solutions of long-chain phosphatidylcholine (PC) lipids and bile salts (BS) are commonly used as model systems for human bile. The detergent bile salts solubilize the non-soluble phospholipids into small mixed micelles (e.g. refs 1-4). This process is essential for the biological role of bile, which is to transport lipids from the liver to the intestine in order to solubilize digestion products and to help eliminate cholesterol from the body. Another important aspect of human bile is its ability to solubilize small amounts of cholesterol (i.e. small with respect to the amount of cholesterol in phospholipid membranes, but still large compared to the solubility of cholesterol in water). When cholesterol levels are too high, cholesterol crystals may nucleate (via intermediate liquid crystalline phases), forming structures that are precursors to gallstone formation. Experimental studies of PC/BS/cholesterol mixtures indicate that mixed micelles can solubilize small amounts of cholesterol without changing the properties of the micelles. The manner in which cholesterol is incorporated at the molecular level is unclear.