Thermodynamic Consideration on Cholesterol-Induced Lateral Phase Separation within Lipid Bilayer Membranes

Abstract

We have so far studied the effect of cholesterol on the bilayer phase behavior of a homologous series of symmetric linear phosphatidylcholines (C_nPC_s) with different chain lengths (n = 14–18) by means of high-sensitivity differential scanning calorimetry and fluorescence spectroscopy using 6-propionyl-2-(N,N-dimethylamino)naphthalene (Prodan) as a membrane probe. The temperature–cholesterol composition (X_ch) phase diagrams constructed for these binary bilayers indicated several important characteristic of the phase behavior of them. First, the phase diagrams are similar to those for the liquid/solid phase equilibria of general binary mixtures that exhibit incongruent melting behavior, suggesting that cholesterol and C_nPC molecules are essentially immiscible within the binary bilayer. Second, a characteristic point like a peritectic point appears on the phase diagram, suggesting that cholesterol has a propensity to form a molecular cluster with its surrounding C_nPC molecules. The X_ch-dependent phase behavior indicated by the phase diagrams, especially cholesterol-induced lateral phase separation, was successfully explained by introducing the so-called superlattice view. In addition, this view allowed us to consider the relationship between the extent of the cholesterol effect and the hydrocarbon-chain length of the host C_nPC molecules.