Biopolym. Cell. 2012; 28(1):24-38.
http://dx.doi.org/10.7124/bc.000029
Огляди
Сучасні уявлення про структуру і динаміку біологічних мембран
1Демченко О. П.
  1. Інститут біохімії ім. О. В. Палладіна НАН України
    вул. Леонтовича, 9, Київ, Україна, 01601

Abstract

Останнім часом відбулися істотні зміни у поглядах на функціонування і структурно-динамічні властивості біологічних мембран. Переглянуто дані щодо ієрархічної кластерної будови мембран і ролі білкових і ліпідних компонентів. Встановлено факт драматичної різниці ліпідного складу між зовнішнім і внутрішнім моношарами плазматичних мембран, який має важливе значення для розуміння мембранних процесів. Зокрема, існують відмінності між моношарами у поверхневому заряді і потенціалі, зв’язуванні іонів, взаємодії з молекулами білків тощо. Гліколіпідний компонент зовнішнього моношару і взаємодія з цитоскелетом внутрішнього моношару дозволяють мембрані через поглиблення асиметрії набути важливих функціональних властивостей. Необхідний більш критичний підхід до результатів, одержаних зі спрощеними аналогами біомембран – ліпідними і білково-ліпідними бішаровими структурами. У спробах описання і моделювання властивостей клітинних мембран існує потреба відходу від двовимірності (що зводить аналіз лише в площину мембрани) і переходу до більш реалістичних тривимірних моделей.
Keywords: біологічні мембрани, мікродомени і рафти, трансмембранний розподіл ліпідів, моделі біомембран
Повний текст: (PDF, українською) (PDF, англійською)

References

[1] Singer S. J., Nicolson G. L. The fluid mosaic model of the structure of cell membranes. Science 1972 175, N 4023:720–731.
[2] Somerharju P., Virtanen J. A.,Cheng K. H. Lateral organisation of membrane lipids. The superlattice view. Biochim. Biophys. Acta 1999 1440, N 1:32–48.
[3] Vereb G., Szollosi J., Matko J., Nagy P., Farkas T., Vigh L., Matyus L., Waldmann T. A., Damjanovich S. Dynamic, yet structured: The cell membrane three decades after the Singer-Nicolson model. Proc. Natl Acad. Sci. USA 2003 100, N 14:8053–8058.
[4] Hancock J. F. Lipid rafts: contentious only from simplistic standpoints. Nat. Rev. Mol. Cell Biol 2006 7, N 6:456–462.
[5] Shaikh S. R., Edidin M. A. Membranes are not just rafts. Chem. Phys. Lipids 2006 144, N 1:1–3.
[6] Kusumi A., Shirai Y. M., Koyama-Honda I., Suzuki K. G., Fujiwara T. K. Hierarchical organization of the plasma membrane: investigations by single-molecule tracking vs. fluorescence correlation spectroscopy. FEBS Lett 2010 584, N 9:1814– 1823.
[7] Nichols B. Cell biology: without a raft. Nature 2005 436, N 7051:638–639.
[8] Munro S. Lipid rafts: elusive or illusive?. Cell 2003 115, N 4:377–388.
[9] Quinn P. J. A lipid matrix model of membrane raft structure. Prog. Lipid Res 2010 49, N 4:390–406.
[10] Frye L. D., Edidin M. The rapid intermixing of cell surface antigens after formation of mouse-human heterokaryons. J. Cell Sci 1970 7, N 2:319–335.
[11] Stefanova I., Horejsi V., Ansotegui I. J., Knapp W., Stockinger H. GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science 1991 254, N 5034:1016–1019.
[12] Brown D. The tyrosine kinase connection: how GPI-anchored proteins activate T cells. Curr. Opin. Immunol 1993 5, N 3:349–354.
[13] Karnovsky M. J., Kleinfeld A. M., Hoover R. L., Klausner R. D. The concept of lipid domains in membranes. J. Cell Biol 1982 94, N 1:1–6.
[14] London E. How principles of domain formation in model membranes may explain ambiguities concerning lipid raft formation in cells. Biochim. Biophys. Acta 2005 1746, N 3:203–220.
[15] Lichtenberg D., Goni F. M., Heerklotz H. Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem. Sci 2005 30, N 8:430–436.
[16] Morris R. J., Jen A., Warley A. Isolation of nano-meso scale detergent resistant membrane that has properties expected of lipid «rafts». J. Neurochem 2011 116, N 5:671–677.
[17] Anderson R. G., Jacobson K. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 2002 296, N 5574:1821–1825.
[18] Brown D. A. Analysis of raft affinity of membrane proteins by detergent-insolubility. Methods Mol. Biol 2007 398:9–20.
[19] Zidovetzki R., Levitan I. Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies. Biochim. Biophys. Acta 2007 1768, N 6:1311–1324.
[20] Shvartsman D. E., Gutman O., Tietz A., Henis Y. I. Cyclodextrins but not compactin inhibit the lateral diffusion of membrane proteins independent of cholesterol. Traffic 2006 7, N 7:917–926.
[21] Chapkin R. S., Wang N., Fan Y. Y., Lupton J. R., Prior I. A. Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim. Biophys. Acta 2008 1778, N 2:466–471.
[22] Marks D. L., Bittman R., Pagano R. E. Use of Bodipy-labeled sphingolipid and cholesterol analogs to examine membrane microdomains in cells. Histochem. Cell Biol 2008 130, N 5:819–832.
[23] Juhasz J., Davis J. H., Sharom F. J. Fluorescent probe partitioning in giant unilamellar vesicles of «lipid raft» mixtures. Biochem. J 2010 430, N 3:415–423.
[24] Gimpl G., Gehrig-Burger K. Probes for studying cholesterol binding and cell biology. Steroids 2011 76, N 3:216–231.
[25] Klymchenko A. S., Stoeckel H., Takeda K., Mely Y. Fluorescent probe based on intramolecular proton transfer for fast ratiometric measurement of cellular transmembrane potential. J. Phys. Chem. B 2006 110, N 27:13624–13632.
[26] Kiss E., Nagy P., Balogh A., Szollosi J., Matko J. Cytometry of raft and caveola membrane microdomains: from flow and imaging techniques to high throughput screening assays. Cytometry A 2008 73, N 7:599–614.
[27] Garcia-Saez A. J., Schwille P. Surface analysis of membrane dynamics. Biochim. Biophys. Acta 2010 1798, N 4:766–776.
[28] Eggeling C., Ringemann C., Medda R., Schwarzmann G., Sandhoff K., Polyakova S., Belov V. N., Hein B., von Middendorff C., Schonle A., Hell S. W. Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 2009 457, N 7233:1159–1162.
[29] Wenger J., Conchonaud F., Dintinger J., Wawrezinieck L., Ebbesen T. W., Rigneault H., Marguet D., Lenne P. F. Diffusion analysis within single nanometric apertures reveals the ultrafine cell membrane organization. Biophys. J 2007 92, N 3:913–919.
[30] van Zanten T. S., Cambi A., Garcia-Parajo M. F. A nanometer scale optical view on the compartmentalization of cell membranes. Biochim. Biophys. Acta 2010 1798, N 4:777–787.
[31] Day C. A., Kenworthy A. K. Tracking microdomain dynamics in cell membranes. Biochim. Biophys. Acta 2009 1788, N 1:245–253.
[32] Ritchie K., Shan X. Y., Kondo J., Iwasawa K., Fujiwara T., Kusumi A. Detection of non-Brownian diffusion in the cell membrane in single molecule tracking. Biophys. J 2005 88, N 3:2266–2277.
[33] He H. T., Marguet D. Detecting nanodomains in living cell membrane by fluorescence correlation spectroscopy. Annu. Rev. Phys. Chem 2011 62:417–436.
[34] Wawrezinieck L., Rigneault H., Marguet D., Lenne P. F. Fluorescence correlation spectroscopy diffusion laws to probe the submicron cell membrane organization. Biophys. J 2005 89, N 6:4029–4042.
[35] Loura L. M., de Almeida R. F., Silva L. C., Prieto M. FRET analysis of domain formation and properties in complex membrane systems. Biochim. Biophys. Acta 2009 1788, N 1:209–224.
[36] Rao M., Mayor S. Use of Forster’s resonance energy transfer microscopy to study lipid rafts. Biochim. Biophys. Acta 2005 1746, N 3:221–233.
[37] Levitt J. A., Matthews D. R., Ameer-Beg S. M., Suhling K. Fluorescence lifetime and polarization-resolved imaging in cell biology. Curr. Opin. Biotechnol 2009 20, N 1:28–36.
[38] de Almeida R. F., Loura L. M., Prieto M. Membrane lipid domains and rafts: current applications of fluorescence lifetime spectroscopy and imaging. Chem. Phys. Lipids 2009 157, N 2:61–77.
[39] Gavutis M., Lata S., Piehler J. Probing 2-dimensional proteinprotein interactions on model membranes. Nat. Protoc 2006 1, N 4:2091–2103.
[40] Bagatolli L. A., Ipsen J. H., Simonsen A. C., Mouritsen O. G. An outlook on organization of lipids in membranes: searching for a realistic connection with the organization of biological membranes. Prog. Lipid Res 2010 49, N 4:378–389.
[41] Almeida P. F., Pokorny A., Hinderliter A. Thermodynamics of membrane domains. Biochim. Biophys. Acta 2005 1720, N 1–2:1–13.
[42] Turner M. S., Sens P., Socci N. D. Nonequilibrium raftlike membrane domains under continuous recycling. Phys. Rev. Lett 2005 95, N 16 168301.
[43] Perlmutter J. D., Sachs J. N. Interleaflet interaction and asymmetry in phase separated lipid bilayers: molecular dynamics simulations. J. Am. Chem. Soc 2011 133, N 17:6563– 6577.
[44] Silva L. C., Futerman A. H., Prieto M. Lipid raft composition modulates sphingomyelinase activity and ceramide-induced membrane physical alterations. Biophys. J 2009 96, N 8:3210–3222.
[45] Nicolini C., Baranski J., Schlummer S., Palomo J., Lumbierres-Burgues M., Kahms M., Kuhlmann J., Sanchez S., Gratton E., Waldmann H., Winter R. Visualizing association of N-ras in lipid microdomains: influence of domain structure and interfacial adsorption. J. Am. Chem. Soc 2006 128, N 1:192–201.
[46] Marsh D. Protein modulation of lipids, and vice-versa, in membranes. Biochim. Biophys. Acta 2008 1778, N 7–8:1545– 1575.
[47] Bacia K., Schuette C. G., Kahya N., Jahn R., Schwille P. SNAREs prefer liquid-disordered over «raft» (liquid-ordered) domains when reconstituted into giant unilamellar vesicles. J. Biol. Chem 2004 279, N 36:37951–37955.
[48] Lingwood D., Ries J., Schwille P., Simons K. Plasma membranes are poised for activation of raft phase coalescence at physiological temperature. Proc. Natl Acad. Sci. USA 2008 105, N 29:10005–10010.
[49] Baumgart T., Hammond A. T., Sengupta P., Hess S. T., Holowka D. A., Baird B. A., Webb W. W. Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles. Proc. Natl Acad. Sci. USA 2007 104, N 9:3165– 3170.
[50] Veatch S. L., Cicuta P., Sengupta P., Honerkamp-Smith A., Holowka D., Baird B. Critical fluctuations in plasma membrane vesicles. ACS Chem. Biol 2008 3, N 5:287–293.
[51] Fantini J., Barrantes F. J. Sphingolipid/cholesterol regulation of neurotransmitter receptor conformation and function. Biochim. Biophys. Acta 2009 1788, N 11:2345–2361.
[52] Loor F. Plasma membrane and cell cortex interactions in lymphocyte functions. Adv. Immunol 1980 30:1–120.
[53] Spiegel S., Kassis S., Wilchek M., Fishman P. H. Direct visualization of redistribution and capping of fluorescent gangliosides on lymphocytes. J. Cell Biol 1984 99, N 5:1575–1581.
[54] Delaunay J. L., Breton M., Trugnan G., Maurice M. Differential solubilization of inner plasma membrane leaflet components by Lubrol WX and Triton X-100. Biochim. Biophys. Acta 2008 1778, N 1:105–112.
[55] Boon J. M., Smith B. D. Chemical control of phospholipid distribution across bilayer membranes. Med. Res. Rev 2002 22, N 3:251–281.
[56] Seigneuret M., Devaux P. F. ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc. Natl Acad. Sci. USA 1984 81, N 12:3751–3755.
[57] McIntyre J. C., Sleight R. G. Fluorescence assay for phospholipid membrane asymmetry. Biochemistry 1991 30, N 51:11819–11827.
[58] Ramirez D. M., Ogilvie W. W., Johnston L. J. NBD-cholesterol probes to track cholesterol distribution in model membranes. Biochim. Biophys. Acta 2010 1798, N 3:558–568.
[59] Best M. D., Rowland M. M., Bostic H. E. Exploiting bioorthogonal chemistry to elucidate protein-lipid binding interactions and other biological roles of phospholipids. Acc. Chem. Res 2011 44, N 9:686–698.
[60] van Engeland M., Nieland L. J., Ramaekers F. C., Schutte B., Reutelingsperger C. P. Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 1998 31, N 1:1–9.
[61] Ohno-Iwashita Y., Shimada Y., Hayashi M., Iwamoto M., Iwashita S., Inomata M. Cholesterol-binding toxins and anti-cholesterol antibodies as structural probes for cholesterol localization. Subcell. Biochem 2010 51:597–621.
[62] Chap H. J., Zwaal R. F., van Deenen L. L. Action of highly purified phospholipases on blood platelets. Evidence for an asymmetric distribution of phospholipids in the surface membrane. Biochim. Biophys. Acta 1977 467, N 2:146–164.
[63] Zachowski A. Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem. J 1993 294, Pt 1:1–14.
[64] Kiessling V., Wan C., Tamm L. K. Domain coupling in asymmetric lipid bilayers. Biochim. Biophys. Acta 2009 1788, N 1:64–71.
[65] Rog T., Pasenkiewicz-Gierula M., Vattulainen I., Karttunen M. Ordering effects of cholesterol and its analogues. Biochim. Biophys. Acta 2009 1788, N 1:97–121.
[66] Wang T. Y., Silvius J. R. Cholesterol does not induce segregation of liquid-ordered domains in bilayers modeling the inner leaflet of the plasma membrane. Biophys. J 2001 81, N 5:2762– 2773.
[67] Martinez-Seara H., Rog T., Pasenkiewicz-Gierula M., Vattulainen I., Karttunen M., Reigada R. Interplay of unsaturated phospholipids and cholesterol in membranes: effect of the doublebond position. Biophys. J 2008 95, N 7:3295–3305.
[68] Di Paolo G., De Camilli P. Phosphoinositides in cell regulation and membrane dynamics. Nature 2006 443, N 7112:651–657.
[69] Fadeel B., Xue D. The ins and outs of phospholipid asymmetry in the plasma membrane: roles in health and disease. Crit. Rev. Biochem. Mol. Biol 2009 44, N 5:264–277.
[70] Mesmin B., Maxfield F. R. Intracellular sterol dynamics. Biochim. Biophys. Acta 2009 1791, N 7:636–645.
[71] Lange Y., Steck T. L. Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol. Prog. Lipid Res 2008 47, N 5:319–332.
[72] Epand R. M. Proteins and cholesterol-rich domains. Biochim. Biophys. Acta 2008 1778, N 7–8:1576–1582.
[73] Contreras F. X., Sanchez-Magraner L., Alonso A., Goni F. M. Transbilayer (flip-flop) lipid motion and lipid scrambling in membranes. FEBS Lett 2010 584, N 9:1779–1786.
[74] Poulsen L. R., Lopez-Marques R. L., Palmgren M. G. Flippases: still more questions than answers. Cell. Mol. Life Sci 2008 65, N 20:3119–3125.
[75] Devaux P. F., Herrmann A., Ohlwein N., Kozlov M. M. How lipid flippases can modulate membrane structure. Biochim. Biophys. Acta 2008 1778, N 7–8:1591–1600.
[76] Demchenko A. P., Yesylevskyy S. O. Nanoscopic description of biomembrane electrostatics: results of molecular dynamics simulations and fluorescence probing. Chem. Phys. Lipids 2009 160, N 2:63–84.
[77] Pohl A., Lopez-Montero I., Rouviere F., Giusti F., Devaux P. F. Rapid transmembrane diffusion of ceramide and dihydroceramide spin-labelled analogues in the liquid ordered phase. Mol. Membr. Biol 2009 26, N 3:194–204.
[78] Bennett W. F., MacCallum J. L., Hinner M. J., Marrink S. J., Tieleman D. P. Molecular view of cholesterol flip-flop and chemical potential in different membrane environments. J. Am. Chem. Soc 2009 131, N 35:12714–12720.
[79] Sanyal S., Menon A. K. Flipping lipids: why an’ what’s the reason for?. ACS Chem. Biol 2009 4, N 11:895–909.
[80] Collins M. D. Interleaflet coupling mechanisms in bilayers of lipids and cholesterol. Biophys. J 2008 94, N 5:L32–34.
[81] Collins M. D., Keller S. L. Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers. Proc. Natl Acad. Sci. USA 2008 105, N 1:124–128.
[82] Putzel G. G., Schick M. Phase behavior of a model bilayer membrane with coupled leaves. Biophys. J 2008 94, N 3:869–877.
[83] Horner A., Antonenko Y. N., Pohl P. Coupled diffusion of peripherally bound peptides along the outer and inner membrane leaflets. Biophys. J 2009 96, N 7:2689–2695.
[84] Gri G., Molon B., Manes S., Pozzan T., Viola A. The inner side of T cell lipid rafts. Immunol. Lett 2004 94, N 3:247–252.
[85] Wu M., Holowka D., Craighead H. G., Baird B. Visualization of plasma membrane compartmentalization with patterned lipid bilayers. Proc. Natl Acad. Sci USA 2004 101, N 38:13798– 13803.
[86] Westerlund B., Slotte J. P. How the molecular features of glycosphingolipids affect domain formation in fluid membranes. Biochim. Biophys. Acta 2009 1788, N 1:194–201.
[87] Prinetti A., Loberto N., Chigorno V., Sonnino S. Glycosphingolipid behaviour in complex membranes. Biochim. Biophys. Acta 2009 1788, N 1:184–193.
[88] Mishra S., Joshi P. G. Lipid raft heterogeneity: an enigma. J. Neurochem 2007 103, Suppl 1:135–142.
[89] Valensin S., Paccani S. R., Ulivieri C., Mercati D., Pacini S., Patrussi L., Hirst T., Lupetti P., Baldari C. T. F-actin dynamics control segregation of the TCR signaling cascade to clustered lipid rafts. Eur. J. Immunol 2002 32, N 2:435–446.
[90] Chichili G. R., Rodgers W. Cytoskeleton-membrane interactions in membrane raft structure. Cell. Mol. Life Sci 2009 66, N 14:2319–2328.
[91] Meiri K. F. Membrane/cytoskeleton communication. Subcell. Biochem 2004 37:247–282.
[92] Andrews N. L., Lidke K. A., Pfeiffer J. R., Burns A. R., Wilson B. S., Oliver J. M., Lidke D. S. Actin restricts FcepsilonRI diffusion and facilitates antigen-induced receptor immobilization. Nat. Cell Biol 2008 10, N 8:955–963.
[93] Kabouridis P. S. Lipid rafts in T cell receptor signalling. Mol. Membr. Biol 2006 23, N 1:49–57.
[94] Doherty G. J., McMahon H. T. Mediation, modulation, and consequences of membrane-cytoskeleton interactions. Annu. Rev. Biophys 2008 37:65–95.
[95] Manno S., Takakuwa Y., Mohandas N. Identification of a functional role for lipid asymmetry in biological membranes: Phosphatidylserine-skeletal protein interactions modulate membrane stability. Proc. Natl Acad. Sci. USA 2002 99, N 4:1943– 1948.
[96] Demchenko A. P., Mely Y., Duportail G., Klymchenko A. S. Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes. Biophys. J 2009 96, N 9:3461–3470.
[97] Yeung T., Gilbert G. E., Shi J., Silvius J., Kapus A., Grinstein S. Membrane phosphatidylserine regulates surface charge and protein localization. Science 2008 319, N 5860:210–213.
[98] Gurtovenko A. A., Vattulainen I. Effect of NaCl and KCl on phosphatidylcholine and phosphatidylethanolamine lipid membranes: insight from atomic-scale simulations for understanding salt-induced effects in the plasma membrane. J. Phys. Chem. B 2008 112, N 7:1953–1962.
[99] Gurtovenko A. A.,Vattulainen I. Intrinsic potential of cell membranes: opposite effects of lipid transmembrane asymmetry and asymmetric salt ion distribution. J. Phys. Chem. B 2009 113, N 20:7194–7198.
[100] Lee S. J., Song Y., Baker N. A. Molecular dynamics simulations of asymmetric NaCl and KCl solutions separated by phosphatidylcholine bilayers: potential drops and structural changes induced by strong Na+-lipid interactions and finite size effects. Biophys. J 2008 94, N 9:3565–3576.
[101] Vacha R., Jurkiewicz P., Petrov M., Berkowitz M. L., Bockmann R. A., Barucha-Kraszewska J., Hof M., Jungwirth P. Mechanism of interaction of monovalent ions with phosphatidylcholine lipid membranes. J. Phys. Chem. B 2010 114, N 29:9504– 9509.
[102] Demchenko A. P. Introduction to fluorescence sensing Amsterdam: Springer, 2009 590 p.
[103] Demchenko A. P. The concept of lambda-ratiometry in fluorescence sensing and imaging. J. Fluoresc 2010 20, N 5:1099– 1128.
[104] Klymchenko A. S., Duportail G., Ozturk T., Pivovarenko V. G., Mely Y., Demchenko A. P. Novel two-band ratiometric fluorescence probes with different location and orientation in phospholipid membranes. Chem. Biol 2002 9, N 11:1199–1208.
[105] Millard A. C., Jin L., Wei M. D., Wuskell J. P., Lewis A., Loew L. M. Sensitivity of second harmonic generation from styryl dyes to transmembrane potential. Biophys. J 2004 86, N 2:1169–1176.
[106] Jin L., Millard A. C., Wuskell J. P., Dong X., Wu D., Clark H. A., Loew L. M. Characterization and application of a new optical probe for membrane lipid domains. Biophys. J 2006 90, N 7:2563–2575.
[107] Kim H. M., Choo H. J., Jung S. Y., Ko Y. G., Park W. H., Jeon S. J., Kim C. H., Joo T., Cho B. R. A two-photon fluorescent probe for lipid raft imaging: C-laurdan. Chembiochem 2007 8, N 5:553–559.
[108] Kim H. M., Jeong B. H., Hyon J. Y., An M. J., Seo M. S., Hong J. H., Lee K. J., Kim C. H., Joo T., Hong S. C., Cho B. R. Twophoton fluorescent turn-on probe for lipid rafts in live cell and tissue. J. Am. Chem. Soc 2008 130, N 13:4246–4247.
[109] Shynkar V. V., Klymchenko A. S., Kunzelmann C., Duportail G., Muller C. D., Demchenko A. P., Freyssinet J. M., Mely Y. Fluorescent biomembrane probe for ratiometric detection of apoptosis. J. Am. Chem. Soc 2007 129, N 7:2187–2193.
[110] Goldenberg N. M., Steinberg B. E. Surface charge: a key determinant of protein localization and function. Cancer Res 2010 70, N 4:1277–1280.
[111] Hynes R. O. Integrins: bidirectional, allosteric signaling machines. Cell 2002 110, N 6:673–687.
[112] Chichili G. R., Westmuckett A. D., Rodgers W. T cell signal regulation by the actin cytoskeleton. J. Biol. Chem 2010 285, N 19:14737–14746.
[113] Yokosuka T., Saito T. The immunological synapse, TCR microclusters, and T cell activation. Curr. Top. Microbiol. Immunol 2010 340:81–107.
[114] van Meer G. Cellular lipidomics. EMBO J 2005 24, N 18:3159–3165.