Phase boundaries and biological membranes

Abstract

Bilayer mixtures of lipids are used by many researchers as chemically simple models for biological membranes. In particular, observations on three-component bilayer mixtures containing cholesterol show rich phase behavior, including several regions of two-phase coexistence and one region of three-phase coexistence. Yet, the relationship between these simple model mixtures and biological membranes, which contain hundreds of different proteins and lipids, is not clear. Many of the model mixtures have been chosen for study because they exhibit readily observed phase separations, not because they are good mimics of cell membrane components. If the many components of cell membranes could be grouped in some way, then understanding the phase behaviors of biological membranes might be enhanced. Furthermore, if the underlying interaction energies between lipids and proteins can be determined, then it might be possible to model the distributions of lipids and proteins in a bilayer membrane, even in complex mixtures.

Figure 1

Only two general types of phase diagrams are needed to describe all of the phase behavior observed so far for three-component lipid mixtures containing cholesterol that show phase coexistence. In addition to cholesterol, the other two components are a lipid whose fully hydrated bilayers are in a gel phase (Lβ or Lβ′) at the measurement temperature (solid lipid), and a lipid whose fully hydrated bilayers are in a liquid-disordered phase (Lα) at the measurement temperature (fluid lipid). (a) The Type I phase diagram has two regions of macroscopic two-phase coexistence. At high cholesterol concentrations, crystals of cholesterol monohydrate coexist with the liquid-ordered phase, Lo. At lower cholesterol concentrations, Lα and Lβ phases coexist. Proposed tielines are shown. (b) The Type II phase diagram has three regions of macroscopic two-phase coexistence, and one region of three-phase coexistence. In addition to the same two-phase regions seen in the Type I diagrams, there is a large two-phase coexistence region where Lα + Lo phases coexist. In addition, a triangle of three-phase coexistence is also seen in which Lα Lo + Lβ phases coexist. Tielines are shown in all of the regions of two-phase coexistence.