Ceramide-1-phosphate, in contrast to ceramide, is not segregated into lateral lipid domains in phosphatidylcholine bilayers.
Sphingolipids are key lipid regulators of cell viability: ceramide is one of the key molecules in inducing programmed cell death (apoptosis), whereas other sphingolipids, such as ceramide 1-phosphate, are mitogenic. The thermotropic and structural behavior of binary systems of N-hexadecanoyl-D-erythro-ceramide (C(16)-ceramide) or N-hexadecanoyl-D-erythro-ceramide-1-phosphate (C(16)-ceramide-1-phosphate; C(16)-C1P) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was studied with DSC and deuterium nuclear magnetic resonance ((2)H-NMR). Partial-phase diagrams (up to a mole fraction of sphingolipids X = 0.40) for both mixtures were constructed based on DSC and (2)H-NMR observations. For C(16)-ceramide-containing bilayers DSC heating scans showed already at X(cer) = 0.025 a complex structure of the main-phase transition peak suggestive of lateral-phase separation. The transition width increased significantly upon increasing X(cer), and the upper-phase boundary temperature of the mixture shifted to approximately 65 degrees C at X(cer) = 0.40. The temperature range over which (2)H-NMR spectra of C(16)-ceramide/DPPC-d(62) mixtures displayed coexistence of gel and liquid crystalline domains increased from approximately 10 degrees for X(cer) = 0.1 to approximately 21 degrees for X(cer) = 0.4. For C16-C1P/DPPC mixtures, DSC and (2)H-NMR observations indicated that two-phase coexistence was limited to significantly narrower temperature ranges for corresponding C1P concentrations. To complement these findings, C(16)-ceramide/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and C16-C1P/POPC mixtures were also studied by (2)H-NMR and fluorescence techniques. These observations indicate that DPPC and POPC bilayers are significantly less perturbed by C(16)-C1P than by C(16)-ceramide and that C(16)-C1P is miscible within DPPC bilayers at least up to X(C1P) = 0.30.
Morrow
Michael R
MR
Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Helle
Anne
A
Perry
Joshua
J
Vattulainen
Ilpo
I
Wiedmer
Susanne K
SK
Holopainen
Juha M
JM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002518:Ceramides / Q000737:chemistry*; D003903:Deuterium; D004161:Diphenylhexatriene / Q000737:chemistry; D005454:Fluorescence Polarization; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D013696:Temperature
D002518:Ceramides; D008051:Lipid Bilayers; D008081:Liposomes; C065576:ceramide 1-phosphate; D004161:Diphenylhexatriene; D015060:1,2-Dipalmitoylphosphatidylcholine; C097760:N-palmitoylsphingosine; D003903:Deuterium