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Biophysical Journal

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phosphatidic-acid, ceramide 1-phosphate, lysophosphatidic acid, sphingomyelinase-d, bilayers, kinase, phase, nmr, phosphatidylcholine, electrostatics




Ceramide-1-phosphate (Cer-1-P), one of the simplest of all sphingophospholipids, occurs in minor amounts in biological membranes. Yet recent evidence suggests important roles of this lipid as a novel second messenger with crucial tasks in cell survival and inflammatory responses. We present a detailed description of the physical chemistry of this hitherto little explored membrane lipid. At full hydration Cer-1-P forms a highly organized subgel (crystalline) bilayer phase (L-c) at low temperature, which transforms into a regular gel phase (L-beta) at similar to 45 degrees C, with the gel to fluid phase transition (L-beta-L-alpha) occurring at similar to 65 degrees C. When incorporated at 5 mol % in a phosphatidylcholine bilayer, the pK(a2) of Cer-1-P, 7.39 +/- 0.03, lies within the physiological pH range. Inclusion of phosphatidylethanolamine in the phosphatidylcholine bilayer, at equimolar ratio, dramatically reduces the pKa2 to 6.64 +/- 6 0.03. We explain these results in light of the novel electrostatic/hydrogen bond switch model described recently for phosphatidic acid. In mixtures with dielaidoylphosphatidylethanolamine, small concentrations of Cer-1-P cause a large reduction of the lamellar-to-inverted hexagonal phase transition temperature, suggesting that Cer-1-P induces, like phosphatidic acid, negative membrane curvature in these types of lipid mixtures. These properties place Cer-1-P in a class more akin to certain glycerophospholipids (phosphatidylethanolamine, phosphatidic acid) than to any other sphingolipid. In particular, the similarities and differences between ceramide and Cer-1-P may be relevant in explaining some of their physiological roles.


Copyright 2007 Biophysical Society. Available on publisher's site at

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