DOES CHOLESTEROL DISCRIMINATE BETWEEN SPHINGOMYELIN AND PHOSPHATIDYLCHOLINE IN MIXED MONOLAYERS CONTAINING BOTH PHOSPHOLIPIDS

The objective of this work was to examine the interaction of cholester ol with both phosphatidylcholines, 1-palmitoyl-2-oleoyl-sn-glycero-3-p hosphocholine (POPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (D PPC), and sphingomyelins, N-oleoyl-D-sphingomyelin (O-SPM) or N-palmit oyl-D-sphingomyelin (P-SPM), in monolayers at an air/water interface. We used cholesterol oxidase to probe for the relative strength of ster ol-phospholipid interaction, and fluorescence microscopy to visualize lateral domain formation in the mixed monolayers. The ternary mixed mo nolayers, which contained cholesterol, POPC, and O-SPM had a twofold h igher average oxidation rate than the corresponding system containing DPPC and P-SPM. This difference in oxidation rate between saturated an d unsaturated systems was observed irrespective of the ratio between p hosphatidylcholine and sphingomyelin in the monolayer. With either the saturated or the unsaturated systems, however, the rate of oxidation was influenced by the ratio of phosphatidylcholine to sphingomyelin. A s the monolayer content of phosphatidylcholine increased and the sphin gomyelin content decreased correspondingly (to maintain a constant cho lesterol-to-phospholipid molar ratio), an increase in the average oxid ation rate was seen in both saturated and mono-unsaturated monolayer s ystems. The relationship between the rate of cholesterol oxidation and the phosphatidylcholine/sphingomyelin ratio was not linear? suggestin g a preferential interaction of cholesterol with sphingomyelin even wh en phosphatidylcholine was present in the monolayer. The formation and stability of cholesterol-rich lateral (liquid-condensed) domains in t he monolayers, as determined by monolayer fluorescence microscopy, was found to be highly influenced by the phospholipid class, the degree o f acyl chain saturation, and by the ratio of phosphatidylcholine to sp hingomyelin in the monolayer. The differences in cholesterol oxidation rates and lateral domain formation, as a function of the ratio of two phospholipids in the monolayers, apparently derived from differences in the hydrophobic interactions between the lipids.