The Lipid Raft Hypothesis: Origins, Obscurities, and Opinions

Abstract

The plasma membrane has long been conceived as a homogenous lipid bilayer sheet that serves as a passive viscous matrix for membrane proteins. The hypothesis of lipid rafts has added more complexity in the lateral organization of the plasma membrane. Lipid rafts were originally defined as micrometer-sized lipid domains enriched in sphingolipids and cholesterol within cellular membranes that assemble specific sets of glycosylphosphatidylinositol-anchored and transmembrane proteins. These domains form platforms for membrane sorting in targeted-membrane trafficking and cell signaling processes. Experimentally, lipid rafts are partially resistant to non-ionic detergent solubilization in the cold and functionally dependent of the cholesterol level in the membrane. The extensive use of these simplistic biochemical definitions has accumulated a large body of inconsistent data that obscure the very concept of lateral membrane organization. More recent studies using less perturbing techniques in living cells have reshaped our understanding in the structure, function and dynamics of the plasma membrane. This current understanding became the essential principles of lateral membrane organization models that add new aspects previously uncovered by the original hypothesis of lipid rafts.