Molecular interactions between lecithin and sphingomyelin. Temperature- and composition-dependent phase separation.

X-ray diffraction, scanning calorimetry, and polarizing light microscopy have used to determine the complete ternary phase diagram egg yolk lecithin/bovine brain sphingomyelin/water over the temperature range 10-44 degrees. The phase diagram shows that lateral separation of phospholipid bilayer phases can arise from variations in both composition and temperature. At 44 degrees in excess water, lecithin and sphingomyelin are miscible at all ratios in a lamellar liquid crystal bilayer phase. For samples containing greater than 33 mol % sphingomyelin, colling to 20 degrees results in the progressive lateral separation of an ordered chain sphingomyelin lamellar gel phase from the lecithin/sphingomyelin liquid crystal bilayer phase. At 20 degrees and below, the spingomyelin gel phase co-exists with an ordered bilayer phase, a stoichiometric peritectic molecular compound (66 mol % lecithin, 33 mol % sphingomyelin). Cooling mixtures containing less than 33 mol % sphingomyelin ultimately separates the compound from a lecithin liquid crystal bilayer phase containing small amounts of sphingomyelin. Although singificant variations in the lecithin/sphingomyelin ratio occur in normal and pathological membranes, at 37 degrees our results would suggest complete bilayer phase and lateral phase separation of the "ordered" sphingomyelin gel phase appears uplikely.