Lipid rafts: A personal account

Abstract

The lipid raft concept of membrane sub-compartmentalizationwas introduced in 1997 and originated from studies on epithelial cell surface polarity. It was the first time that membrane lipid specificity was incorporated into the mechanisms that generate cell architecture. From its epithelial origins, the raft concept was generalized to explain howcells manage to perform their full spectrum of membrane functions. The associative capability of saturated sphingolipids and phospholipids with cholesterol and their repulsion of polyunsaturated membrane lipids formed the basis of the raft concept. With the demonstration that isolated plasma membrane vesicles can separate into two phases by liquid-liquid demixing, this became the physicochemical principle underlying raft sub-compartmentalization. The compartmentalization achieved by clustering fluctuating raft assemblies in living cells could be called an abortive nonequilibrium phase separation. Moreover, recent data demonstrate that raft lipids and proteins form collective cooperatives with emerging properties that enrich their functional repertoire. Together these features provide a new perspective on cell membrane function.