Evidence for condensed lipid/cholesterol complexes in lipid membranes.

Certain binary mixtures of phospholipids and cholesterol exhibit phase diagrams with two immiscibility regions with a sharp cusp in between. The cusp has been suggested to represent the stoichiometry of phospholipid/cholesterol complexes, and cholesterol is thought to exist in two states: a bound, low activity state, and an unbound, high activity state. To better understand the interaction between phospholipids and cholesterol, we have studied the effect of a possible displacing agent, hexadecanol, on the behavior of the binary mixture. Our cholesterol desorption assays indicate that hexadecanol can displace cholesterol from its association with phospholipids, thereby activating it. Phospholipid/cholesterol/hexadecanol systems in which a fraction of cholesterol is replaced by the alcohol have phase diagrams that mimic those of binary systems with the same apparent molar stoichiometry. X-ray data show a broad Bragg peak in these binary systems, indicating that order in these complexes extend over only several molecular dimensions.