Lipid Domains and the Raft Hypothesis

The study of the cell membrane is an old area of research, going back to the origins of cell biology however, there have been some revolutionary advances relatively recently in how we understand the function and structure of living membranes. So much research interest has been generated on this topic recently that it is worthwhile discussing the subject here. 

Until the 1990s, the most widely accepted model for the cell membrane was the fluid mosaic model. In this model, lipids and embedded membrane proteins were described as randomly distributed, with no particular in-plane distribution. This model is now considered simplistic, and current thinking is that biological membranes have a complicated in-plane organization. It is a controversial question whether the thermodynamic phase behavior of the constituent membrane lipids can play an important role in membrane function, and a large amount of literature on the subject has been written. 

This new hypothesis for the structure of the cell membrane relies on the phase behavior of mixed-lipid bilayers phase separation of the lipids influences the organization of membrane proteins and ultimately their function. It is proposed that membrane proteins spatially cluster as a result of favorable interactions with lipid patches in the membrane of differing composition to the surrounding regions. This is known as the 

The idea of spontaneous membrane phase separation being linked to cellular function was first introduced as recently as the late 1990s. In their influential article, Simons and Ikonen described how certain mixtures of lipids can form in-plane bilayer domains. Phase separation is common in mixed systems, where the constituent molecules may have different affinities for each other. In a phase-separated system, two different phases can simultaneously occur at the same temperature in a material, usually with differing molecular compositions. Consider the simple example of oil and water. Given enough thermal energy, they will mix however, below a certain temperature, total phase separation will occur. 

The compositional phase diagram for lipid mixtures can be complicated, with regions of two-phase and three-phase coexistence. Most notably, a new fluid-like phase, the / (liquid ordered) phase has been defined in these mixtures, with increased chain ordering in comparison to the 

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