Phase Segregation on Different Length Scales in a Model Cell Membrane System

Lipid rafts are sphingolipid- and cholesterol-enriched domains on cell membranes that have been implicated in many biological functions, especially in T lymphocytes. We used a field theory to examine the forces underlying raft formation on resting living cell membranes. We find that it is difficult to reconcile the observed size of rafts on living cell membranes (∼100 nm) with a mechanism that involves coupling between spontaneous curvature differences and concentration fluctuations. Such a mechanism seems to predict raft domain sizes that are larger and commensurate with those observed on synthetic membranes. Therefore, using a Poisson-Boltzmann approach, we explore whether electrostatic forces originating from transmembrane proteins and net negative charges on cell membranes could play a role in determining the raft size in living cell membranes. We find that a balance among the intrinsic tendency of raft components to segregate, the line tension, and the effective dipolar interactions among membrane constituents leads to a stable phase with a characteristic length scale commensurate with the observed size of rafts on living cell membranes. We calculate the phase diagram of a system in which these three types of forces are important. In a certain region of the parameter space, an interesting phase with mosaic-like morphology consisting of an intertwined pattern of raft and nonraft domains is predicted. Experiments that could further assess the importance of dipolar interactions for lateral organization of the components on multiple length scales in membranes are suggested.