The concept of lipid domains in membranes

In the past two decades or so there has been considerable advance in our knowledge of membrane structure. The fluid mosaic model of Singer and Nicolson (1) has had great heuristic value in thinking about membrane topology. In this model both proteins and lipids are free to diffuse in the bilayer, implying a random organization of protein and lipid. However, experimental evidence in diverse types of membranes and for several protein entities indicates that the lateral motion of most proteins is not determined primarily by free diffusion through a two-dimensional viscous fluid, but is constrained, probably by mechanisms such as interactions with cytoskeletal components. We will here present our evidence that lipids may also have nonhomogeneity in their lateral distribution, i.e., the lipid may be organized in domains, and that such organizational heterogeneity may have functional as well as structural significance. Although somewhat controversial, it is not inconceivable that proteins could order the packing of surrounding lipids by cooperative types of interactive forces (2), perhaps to a distance of ~50 A. Domains could also be created by the segregation of the lipid components themselves. Lateral phase separations have been demonstrated in liquid-liquid and liquid-gel mixed systems (3), and cholesterol may play a role in such phase separations (4). Another suggested cause of lateral phase separation of lipids is a physical alteration in the membrane structure, such as a change in the radius of curvature (5). Transmembrane lipid asymmetry (6) in itself could create anisotropic forces that could induce imperfect lipid mixing. Evidence for heterogeneity of lateral organization has been adduced in a variety of studies, including x-ray diffraction (7), electron microscopy (8), lateral diffusion measurements (9), differential partitioning of lipid probes (10, 11), differential scanning calorimetry (12), and spin-label measurements (13). We here present our own studies in support of the concept of membrane lipid domains.