Because of recent assertions by a group of investigators that structures called "lamellae" instead of mixed micelles are present in human bile, the nature of biliary cholesterol solubilization and transport ("carriage") has again become a matter of dispute. "Lamellae" are rod- or tubular- shaped banded images observed when biles are negatively stained and dehydrated during electron microscopy; they are believed to be composed principally of biliary phospholipid (which is mostly lecithin) and cholesterol. It is well known that when mixed together in aqueous systems, lecithin and cholesterol, which are otherwise insoluble amphiphilic lipids, swell to form stacked or multilamellar liquid crystals that have regular periodicity because of the bilayer arrangement of the molecules. Provided super-micellar concentrations of cholesterol are present, multilamellar vesicles occur spontaneously in concentrated model biles, and are a frequent occurrence in human gallbladder biles that are beginning to nucleate cholesterol crystals. When multilamellar vesicles are negatively stained and dehydrated, they produce "lamellae" images by electron microscopy. Coincidentally, images of "lamellae" are also produced when purely micellar bile, either model or native is treated similarly. In this review we show that these images are an artifact. This artifact is produced by the dehydration process itself and is due to a phase change i.e. a change in molecular packing which is predicted by the appropriate phase diagram. As a consequence, a dehydrated "lamellae" phase results and the overall effect is an electron microscopic image that is identical to those produced by multilamellar vesicles in supersaturated or lithogenic biles.(ABSTRACT TRUNCATED AT 250 WORDS)
