Membrane Organization and Ionization Behavior of the Minor but Crucial Lipid Ceramide-1-Phosphate

• Published in: Biophysical journal Vol. 94; no. 11; pp. 4320 - 4330
• Main Authors: Kooijman, Edgar E., Sot, Jesús, Montes, L.-Ruth, Alonso, Alicia, Gericke, Arne, de Kruijff, Ben, Kumar, Satyendra, Goñi, Felix M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2008; Biophysical Society; The Biophysical Society
• Subjects: 60 APPLIED LIFE SCIENCES; BASIC BIOLOGICAL SCIENCES; BEHAVIOR; Biochemistry; Cellular biology; Ceramides - chemistry; Computer Simulation; Curvature; FLUIDS; GELS; HYDRATION; INCLUSIONS; IONIZATION; Ions; LECITHINS; Lipid Bilayers - chemistry; LIPIDS; Mathematical models; Membrane Fluidity; MEMBRANES; MIXTURES; Models, Chemical; Models, Molecular; Phase transformations; Phase Transition; Phosphates; Phosphatidic acid; Phosphatidylethanolamine; Phospholipids - chemistry; PHYSICAL CHEMISTRY; RANGE; REDUCTION; Static Electricity; TEMPERATURE RANGE 0065-0273 K; TRANSITION TEMPERATURE; VISIBLE RADIATION
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.107.121046

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 β ) at ∼45°C, with the gel to fluid phase transition ( L β – L α ) occurring at ∼65°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 pK a2 to 6.64 ± 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.