Phosphatidylcholesterol bilayers. A model for phospholipid-cholesterol interaction.

Aqueous dispersions of monovalent and divalent cations salts of O-(1,2-dipalmitosyl-sn-glycero-3-phosphoryl)cholesterol form multilamellar vesicles as shown by freeze-fracture electron microscopy, by electron micrographs of the negatively stained liposomes, and by swelling curves of liposomes in hypo-osmotic medium. Differential scanning calorimetry reveals that aqueous dispersions of divalent metal salts of O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)cholesterol undergo a characteristic thermotropic phase transition with a relatively large cooperative unit (n greater than 250 for the calcium salt). In contrast, monovalent cation salts of O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)cholesterol do not show a thermotropic phase transition under comparable conditions. The molecular area of 0-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)cholesterol in a monolayer is the same in the presence and absence of Ca2+, and is virtually equal to the area of an equimolar mixture of dipalmitoyl phosphatidic acid and cholesterol. To account for the novel state induced by Ca2+, on aqueous dispersions of O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)cholesterol (i.e., bilayer organization and highly cooperative phase transition), a linear array model is proposed in which Ca2+ bridges adjacent arrays of O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)cholesterol molecules, thus freezing the acyl chains in their normal state. One of the main corollaries of the model is that the cooperative unit for a thermotropic phase transition is essentially one-dimensional, rather than a two-dimensional matrix. O-(1,2-Dipalmitoyl-sn-glycero-3-phosphoryl)cholesterol is proposed as an orientationally and conformationally restricted analog of glycerophospholipid plus cholesterol in bilayers.