Membrane organization and ionization behavior of the minor but crucial lipid ceramide-1-phosphate.
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 approximately 45 degrees C, with the gel to fluid phase transition (L(beta)-L(alpha)) occurring at approximately 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 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.
Kooijman
Edgar E
EE
Physics Department, Kent State University, Kent, Ohio, USA. e.e.kooijman@gmail.com
Sot
Jesús
J
Montes
L-Ruth
LR
Alonso
Alicia
A
Gericke
Arne
A
de Kruijff
Ben
B
Kumar
Satyendra
S
Goñi
Felix M
FM
D002518:Ceramides / Q000737:chemistry*; D003198:Computer Simulation; D007477:Ions; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular; D044367:Phase Transition; D010743:Phospholipids / Q000737:chemistry*; D055672:Static Electricity
D002518:Ceramides; D007477:Ions; D008051:Lipid Bilayers; D010743:Phospholipids; C065576:ceramide 1-phosphate