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

Abstract

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.

Keywords: extracellular matrix; lipid rafts; membrane asymmetry; membrane domains; membrane dynamics; membrane-associated cytoskeleton.

Figure 1. The Singer-Nicolson Fluid- Mosaic Membrane Model of cell membrane structure as proposed in 1972

In this view of a cell membrane the solid bodies with stippled cut surfaces represent globular integral membrane proteins randomly distributed in the plane of the membrane. Some integral membrane proteins form specific integral protein complexes, as shown in the figure. Integral proteins are represented in a fluid lipid bilayer. The model does not contain other membrane-associated structures or membrane domains (from Singer and Nicolson).

Figure 2. Different examples of cell membrane integral membrane protein lateral mobility as envisioned by Jacobson and colleagues in 1995

Integral membrane protein lateral move-ments are described as: transient confinement by obstacle clusters (A); transient confinement by the cytoskeleton (B); directed motion by attachment to the cytoskeleton (C); and free, random diffusion in the membrane plane (D) (from Jacobson et al.).

Figure 3. An updated Fluid-Mosaic Membrane Model representation that contains membrane domain structures, membrane - associated cytoskeletal and extracellular structures

The cell membrane has been pealed back to the left to reveal the bottom membrane surface and membrane-associated cytoskeletal elements that form barriers (corrals) that limit the lateral motions of some of the integral membrane proteins. In addition, membrane-associated cytoskeletal structures are directly interacting with integral membrane proteins at the inner membrane surface along with matrix components at the outer surface. Although this diagram presents possible mechanisms of integral membrane protein mobility restraint, it does not accurately represent the sizes and structures of integral membrane proteins, lipid domains or membrane-associated cytoskeletal structures.