Modulation of the phase transition behavior of phosphatidylethanolamine by cholesterol and oxysterols

Cholesterol lowers the bilayer to hexagonal phase transition temperature of phosphatidylethanolamines up to a mole fraction of about 0.1. At cholesterol mole fractions above about 0.3, the effect of this sterol is to stabilize the bilayer phase. The relatively weak effects of cholesterol in altering the bilayer to hexagonal phase transition temperature can be explained on the basis of lateral phase separation. This is indicated by the horizontal liquidus line for the gel to liquid-crystalline transition in the phase diagram for mixtures of cholesterol with dielaidoylphosphatidylethanolamine (DEPE) as well as the fact that cholesterol does not greatly decrease the cooperativity of the bilayer to hexagonal phase transition. The enthalpy of this latter transition increased with increasing mole fractions of cholesterol. Two oxidation products of cholesterol are 5-cholesten-3 beta,7 alpha-diol and cholestan-3 beta,5 alpha,6 beta-triol. Compared with cholesterol, 5-cholesten-3 beta,7 alpha-diol had a greater effect in decreasing the bilayer to hexagonal phase transition temperature and broadening this transition. It is suggested that its effectiveness is due to its greater solubility in the DEPE. In contrast, cholestan-3 beta,5 alpha,6 beta-triol raises the bilayer to hexagonal phase transition temperature of DEPE. This is due to its larger and more hydrophilic head group. In addition, its length, being shorter than that of DEPE, would not allow it to pack efficiently in a hexagonal phase arrangement. We suggest that this same effect is responsible for cholesterol raising the bilayer to hexagonal phase transition temperature at higher mole fractions.