Abstract
Biological membranes contain domains having distinct physical properties. We study defined mixtures of phosphoglycerolipids and sphingolipids to ascertain the fundamental interactions governing these lipids in the absence of other cell membrane components. By using (2)H-NMR we have determined the temperature and composition dependencies of membrane structure and phase behavior for aqueous dispersions of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and the ceramide (Cer) N-palmitoyl-sphingosine. It is found that gel and liquid-crystalline phases coexist over a wide range of temperature and composition. Domains of different composition and phase state are present in POPC/Cer membranes at physiological temperature for Cer concentrations exceeding 15 mol %. The acyl chains of liquid crystalline phase POPC are ordered by the presence of Cer. Moreover, Cer's chain ordering is greater than that of POPC in the liquid crystalline phase. However, there is no evidence of liquid-liquid phase separation in the liquid crystalline region of the POPC/Cer phase diagram.
Full Text
The Full Text of this article is available as a PDF (115.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bouwstra J. A., Thewalt J., Gooris G. S., Kitson N. A model membrane approach to the epidermal permeability barrier: an X-ray diffraction study. Biochemistry. 1997 Jun 24;36(25):7717–7725. doi: 10.1021/bi9628127. [DOI] [PubMed] [Google Scholar]
- Carrer D. C., Maggio B. Phase behavior and molecular interactions in mixtures of ceramide with dipalmitoylphosphatidylcholine. J Lipid Res. 1999 Nov;40(11):1978–1989. [PubMed] [Google Scholar]
- Curatolo W. Thermal behavior of fractionated and unfractionated bovine brain cerebrosides. Biochemistry. 1982 Apr 13;21(8):1761–1764. doi: 10.1021/bi00537a010. [DOI] [PubMed] [Google Scholar]
- Dobrowsky R. T. Sphingolipid signalling domains floating on rafts or buried in caves? Cell Signal. 2000 Feb;12(2):81–90. doi: 10.1016/s0898-6568(99)00072-8. [DOI] [PubMed] [Google Scholar]
- Freire E., Bach D., Correa-Freire M., Miller I., Barenholz Y. Calorimetric investigation of the complex phase behavior of glucocerebroside dispersions. Biochemistry. 1980 Aug 5;19(16):3662–3665. doi: 10.1021/bi00557a004. [DOI] [PubMed] [Google Scholar]
- Holopainen J. M., Lehtonen J. Y., Kinnunen P. K. Lipid microdomains in dimyristoylphosphatidylcholine-ceramide liposomes. Chem Phys Lipids. 1997 Aug 8;88(1):1–13. doi: 10.1016/s0009-3084(97)00040-6. [DOI] [PubMed] [Google Scholar]
- Holopainen J. M., Lemmich J., Richter F., Mouritsen O. G., Rapp G., Kinnunen P. K. Dimyristoylphosphatidylcholine/C16:0-ceramide binary liposomes studied by differential scanning calorimetry and wide- and small-angle x-ray scattering. Biophys J. 2000 May;78(5):2459–2469. doi: 10.1016/S0006-3495(00)76790-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holopainen J. M., Subramanian M., Kinnunen P. K. Sphingomyelinase induces lipid microdomain formation in a fluid phosphatidylcholine/sphingomyelin membrane. Biochemistry. 1998 Dec 15;37(50):17562–17570. doi: 10.1021/bi980915e. [DOI] [PubMed] [Google Scholar]
- Hong-wei S., McConnell H. Phase separations in phospholipd membranes. Biochemistry. 1975 Feb 25;14(4):847–854. doi: 10.1021/bi00675a032. [DOI] [PubMed] [Google Scholar]
- Huang H. W., Goldberg E. M., Zidovetzki R. Ceramides modulate protein kinase C activity and perturb the structure of Phosphatidylcholine/Phosphatidylserine bilayers. Biophys J. 1999 Sep;77(3):1489–1497. doi: 10.1016/S0006-3495(99)76996-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang H. W., Goldberg E. M., Zidovetzki R. Ceramides perturb the structure of phosphatidylcholine bilayers and modulate the activity of phospholipase A2. Eur Biophys J. 1998;27(4):361–366. doi: 10.1007/s002490050143. [DOI] [PubMed] [Google Scholar]
- Kirschnek S., Paris F., Weller M., Grassme H., Ferlinz K., Riehle A., Fuks Z., Kolesnick R., Gulbins E. CD95-mediated apoptosis in vivo involves acid sphingomyelinase. J Biol Chem. 2000 Sep 1;275(35):27316–27323. doi: 10.1074/jbc.M002957200. [DOI] [PubMed] [Google Scholar]
- Kitson N., Thewalt J., Lafleur M., Bloom M. A model membrane approach to the epidermal permeability barrier. Biochemistry. 1994 May 31;33(21):6707–6715. doi: 10.1021/bi00187a042. [DOI] [PubMed] [Google Scholar]
- Lafleur M., Fine B., Sternin E., Cullis P. R., Bloom M. Smoothed orientational order profile of lipid bilayers by 2H-nuclear magnetic resonance. Biophys J. 1989 Nov;56(5):1037–1041. doi: 10.1016/S0006-3495(89)82749-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lu D., Singh D., Morrow M. R., Grant C. W. Effect of glycosphingolipid fatty acid chain length on behavior in unsaturated phosphatidylcholine bilayers: a 2H NMR study. Biochemistry. 1993 Jan 12;32(1):290–297. doi: 10.1021/bi00052a037. [DOI] [PubMed] [Google Scholar]
- Maggio B., Ariga T., Sturtevant J. M., Yu R. K. Thermotropic behavior of glycosphingolipids in aqueous dispersions. Biochemistry. 1985 Feb 26;24(5):1084–1092. doi: 10.1021/bi00326a003. [DOI] [PubMed] [Google Scholar]
- Massey J. B. Interaction of ceramides with phosphatidylcholine, sphingomyelin and sphingomyelin/cholesterol bilayers. Biochim Biophys Acta. 2001 Feb 9;1510(1-2):167–184. doi: 10.1016/s0005-2736(00)00344-8. [DOI] [PubMed] [Google Scholar]
- Nezil F. A., Bayerl S., Bloom M. Temperature-reversible eruptions of vesicles in model membranes studied by NMR. Biophys J. 1992 May;61(5):1413–1426. doi: 10.1016/S0006-3495(92)81947-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pilgram G. S., Engelsma-van Pelt A. M., Bouwstra J. A., Koerten H. K. Electron diffraction provides new information on human stratum corneum lipid organization studied in relation to depth and temperature. J Invest Dermatol. 1999 Sep;113(3):403–409. doi: 10.1046/j.1523-1747.1999.00706.x. [DOI] [PubMed] [Google Scholar]
- Ruocco M. J., Atkinson D., Small D. M., Skarjune R. P., Oldfield E., Shipley G. G. X-ray diffraction and calorimetric study of anhydrous and hydrated N-palmitoylgalactosylsphingosine (cerebroside). Biochemistry. 1981 Oct 13;20(21):5957–5966. doi: 10.1021/bi00524a006. [DOI] [PubMed] [Google Scholar]
- Shah J., Atienza J. M., Duclos R. I., Jr, Rawlings A. V., Dong Z., Shipley G. G. Structural and thermotropic properties of synthetic C16:0 (palmitoyl) ceramide: effect of hydration. J Lipid Res. 1995 Sep;36(9):1936–1944. [PubMed] [Google Scholar]
- Thewalt J. L., Bloom M. Phosphatidylcholine: cholesterol phase diagrams. Biophys J. 1992 Oct;63(4):1176–1181. doi: 10.1016/S0006-3495(92)81681-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Veiga M. P., Arrondo J. L., Goñi F. M., Alonso A. Ceramides in phospholipid membranes: effects on bilayer stability and transition to nonlamellar phases. Biophys J. 1999 Jan;76(1 Pt 1):342–350. doi: 10.1016/S0006-3495(99)77201-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Venkataraman K., Futerman A. H. Ceramide as a second messenger: sticky solutions to sticky problems. Trends Cell Biol. 2000 Oct;10(10):408–412. doi: 10.1016/s0962-8924(00)01830-4. [DOI] [PubMed] [Google Scholar]
- Vist M. R., Davis J. H. Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: 2H nuclear magnetic resonance and differential scanning calorimetry. Biochemistry. 1990 Jan 16;29(2):451–464. doi: 10.1021/bi00454a021. [DOI] [PubMed] [Google Scholar]
- Xu X., Bittman R., Duportail G., Heissler D., Vilcheze C., London E. Effect of the structure of natural sterols and sphingolipids on the formation of ordered sphingolipid/sterol domains (rafts). Comparison of cholesterol to plant, fungal, and disease-associated sterols and comparison of sphingomyelin, cerebrosides, and ceramide. J Biol Chem. 2001 Jun 29;276(36):33540–33546. doi: 10.1074/jbc.M104776200. [DOI] [PubMed] [Google Scholar]