Publication Title

Biophysical Journal

Publication Date

6-1-2008

Document Type

Article

DOI

10.1529/biophysj.107.121046

Keywords

phosphatidic acid, ceramide 1 phosphate, lysophosphatidic acid, sphingomyelinase D, bilayers, kinase, phase, Nmr, phosphatidylcholine, electrostatics

Disciplines

Physics

Abstract

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.

Comments

Copyright 2007 Biophysical Society. Available on publisher's site at http://dx.doi.org/10.1529/biophysj.107.121046.


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