Condensed complexes, rafts, and the chemical activity of cholesterol in membranes

Epifluorescence microscopy studies of mixtures of phospholipids and cholest erol at the air-water interface often exhibit coexisting liquid phases. The properties of these liquids point to the formation of "condensed complexes " between cholesterol and certain phospholipids, such as sphingomyelin. It is found that monolayers that form complexes can incorporate a low concentr ation of a ganglioside G(M1). This glycolipid is visualized by using a fluo rescently labeled B subunit of cholera toxin. Three coexisting liquid phase s are found by using this probe together with a fluorescent phospholipid pr obe. The three liquid phases are identified as a phospholipid-rich phase, a cholesterol-rich phase, and a condensed complex-rich phase. The cholera to xin B labeled ganglioside G(M1) is found exclusively in the condensed compl ex-rich phase. Condensed complexes are likely present in animal cell membra nes. where they should facilitate the formation of specialized domains such as rafts. Condensed complexes also have a major effect in determining the chemical activity of cholesterol. It is suggested that this chemical activi ty plays an essential role in the regulation of cholesterol biosynthesis. G radients in the chemical activity of cholesterol should likewise govern the rates and direction of intracellular intermembrane cholesterol transport.