Theory of Raft Formation by the Cross-Linking of Saturated or Unsaturated Lipids in Model Lipid Bilayers

We consider the effect of cross-linking a small fraction of lipids, either saturated or unsaturated, in a mixture of saturated and unsaturated lipids and cholesterol. The change in phase behavior is examined utilizing a recent phenomenological model of the ternary system, which is extended to include a fourth component representing the cross-linked lipids. These lipids are taken to be identical to monomeric ones except for their reduced entropy of mixing. We find that even a relatively small amount of cross-linked lipids, less than 5 mol %, is sufficient to significantly expand the range of compositions within which there is coexistence between liquid-ordered and liquid-disordered phases. Equivalently, the cross-linking of lipids increases the liquid-liquid miscibility transition temperature, and therefore could bring about phase separation at a temperature at which, before cross-linking, there was only a single liquid phase.