Update of the 1972 Singer-Nicolson Fluid-Mosaic Model of Membrane Structure.

The Fluid-Mosaic Membrane Model of cell membrane structure was based on thermodynamic principals and the available data on component lateral mobility within the membrane plane [Singer SJ, Nicolson GL. The Fluid Mosaic Model of the structure of cell membranes. Science 1972; 175: 720-731]. After more than forty years the model remains relevant for describing the basic nano-scale structures of a variety of biological membranes. More recent information, however, has shown the importance of specialized membrane domains, such as lipid rafts and protein complexes, in describing the macrostructure and dynamics of biological membranes. In addition, membrane-associated cytoskeletal structures and extracellular matrix also play roles in limiting the mobility and range of motion of membrane components and add new layers of complexity and hierarchy to the original model. An updated Fluid-Mosaic Membrane Model is described, where more emphasis has been placed on the mosaic nature of cellular membranes where protein and lipid components are more crowded and limited in their movements in the membrane plane by lipid-lipid, protein-protein and lipid-protein interactions as well as cell-matrix, cell-cell and cytoskeletal interactions. These interactions are important in restraining membrane components and maintaining the unique mosaic organization of cell membranes into functional, dynamic domains.