Role of the stereochemistry of the hydroxyl group of cholesterol and the formation of nonbilayer structures in phosphatidylethanolamines

The phase behavior of mixtures of cholesterol or epicholesterol with phosphatidylethanolamine was studied by differential scanning calorimetry and by X-ray diffraction. Discrete domains of cholesterol are detected by X-ray diffraction in the L alpha phase of phosphatidylethanolamine from egg yolk and synthetic dielaidoylphosphatidylethanolamine beginning at mole fractions of 0.35-0.4 cholesterol. Separate domains of crystalline epicholesterol can also be detected in the L alpha phase of dielaidoylphosphatidylethanolamine by X-ray diffraction at as little as 0.16 mole fraction of epicholesterol. This is a result of poor miscibility of the epicholesterol with dielaidoylphosphatidylethanolamine. Epicholesterol does not alter the L beta----L alpha transition or bilayer spacing. Epicholesterol also has little effect on the diameter of the cylinders in the hexagonal phase. Formation of the inverted hexagonal phase is facilitated by addition of small amounts of cholesterol (mole fraction less than 0.2) in both egg phosphatidylethanolamine and dielaidoylphosphatidylethanolamine. However, at higher mole fractions of cholesterol, the stability of the liquid-crystalline phase is found to increase markedly for dielaidoylphosphatidylethanolamine but not for egg phosphatidylethanolamine, indicating the importance of the structure of the acyl chains in controlling the relative stability of the lamellar and nonlamellar phases in these systems. In contrast to cholesterol, epicholesterol markedly lowers the L alpha----HII phase transition temperature at low mole fraction of sterol. This result demonstrates the importance of the orientation and motional properties of an additive in determining the L alpha----HII transition temperature.