Encyclopedia of Biophysics

Living Edition
| Editors: Gordon Roberts, Anthony Watts, European Biophysical Societies

Membrane Lipid Domains

  • José Carlos BozelliJr.
  • Richard M. Epand
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-35943-9_547-1


In living organisms, cells and organelles compartmentalize their contents using semipermeable barriers: those are membranes. It is the presence of membranes that allow the segregation of biochemical reactions for increased metabolic efficiency and control. In addition, membranes allow for the buildup of electrochemical gradients that can be coupled with energy-requiring processes needed for life. Moreover, the molecular components of membranes need to actively take part in signaling and membrane trafficking. In the nineteenth century, permeability studies had shown that cellular membranes were more permeable to hydrophobic molecules than to ions and hydrophilic molecules, which led to the proposition that membranes were made of lipids (defined as hydrophobic molecules, generally soluble in organic solvents, of biological origin) (Edidin 2003). From the discovery that membranes were made of lipids, until the 1970s, there were significant advancements in the field of...

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  1. Almeida PFF (2009) Thermodynamics of lipid interactions in complex bilayers. Biochim Biophys Acta 1788:72–85CrossRefPubMedGoogle Scholar
  2. Almeida PFF, Pokorny A, Hinderliter A (2005) Thermodynamics of membrane domains. Biochim Biophys Acta 1720:1–13CrossRefPubMedGoogle Scholar
  3. Althoff T, Mills DJ, Popot JL, Kühlbrandt W (2011) Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J 30:4652–4664CrossRefPubMedPubMedCentralGoogle Scholar
  4. Baumgart T, Das S, Webb W, Jenkins J (2005) Membrane elasticity in giant vesicles with fluid phase coexistence. Biophys J 89:1067–1080CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bretscher MS (1972) Asymmetrical lipid bilayer structure for biological membranes. Nature New Biol 236:11–12CrossRefPubMedGoogle Scholar
  6. Brown DA, Rose JK (1992) Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68:533–544CrossRefPubMedGoogle Scholar
  7. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318:1258–1265CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chidlow JH Jr, Sessa WC (2010) Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation. Cardiovasc Res 86:219–225CrossRefPubMedPubMedCentralGoogle Scholar
  9. Collins MD, Keller SL (2008) Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers. Proc Natl Acad Sci U S A 105:124–128CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dick RA, Goh SL, Feigenson GW, Vogt VM (2012) HIV-1 Gag protein can sense the cholesterol and acyl chain environment in model membranes. Proc Natl Acad Sci U S A 109:18761–18766CrossRefPubMedPubMedCentralGoogle Scholar
  11. Dietrich C, Yang B, Fujiwara T, Kusumi A, Jacobson K (2002) Relationship of lipid rafts to transient confinement zones detected by single particle tracking. Biophys J 82:274–284CrossRefPubMedPubMedCentralGoogle Scholar
  12. Edidin M (2003) Lipids on the frontier: a century of cell-membrane bilayers. Nat Rev Mol Cell Biol 4:414–418CrossRefPubMedGoogle Scholar
  13. Eggeling C, Ringemann C, Medda R, Schwarzmann G, Sandhoff K, Polyakova S, Belov VN, Hein B, von Middendorff C, Schönle A, Hell SW (2009) Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457:1159–1163CrossRefPubMedGoogle Scholar
  14. Engelman DM (2005) Membranes are more mosaic than fluid. Nature 438:578–580CrossRefPubMedGoogle Scholar
  15. Epand RM, Epand RF (2010) Chapter 7 Biophysical analysis of membrane-targeting antimicrobial peptides: membrane properties and the design of peptides specifically targeting gram-negative bacteria. In: Wang G (ed) Antimicrobial peptides: discovery, design and novel therapeutic strategies, Henderson B, Wilson M (ed) Advances in molecular and cellular microbiology, vol 18. CABI, Wallingford, pp 116–127Google Scholar
  16. Epand RF, Tokarska-Schlattner M, Schlattner U, Wallimann T, Epand RM (2007) Cardiolipin clusters and membrane domain formation induced by mitochondrial proteins. J Mol Biol 365:968–980CrossRefPubMedGoogle Scholar
  17. Epand RM, Thomas A, Brasseur R, Epand RF (2010) Chapter 9 Cholesterol interaction with proteins that partition into membrane domains: an overview. In: Harris JR, (ed) Cholesterol binding and cholesterol transport proteins, Subcellular biochemistry, vol 51. Harris JR, Quinn PJ, (ed) Springer, Heidelberg, pp 253–278Google Scholar
  18. Ewers H, Römer W, Smith AE, Bacia K, Dmitrieff S, Chai W, Mancini R, Kartenbeck J, Chambon V, Berland L, Oppenheim A, Schwarzmann G, Feizi T, Schwille P, Sens P, Helenius A, Johannes L (2010) GM1 structure determines SV40-induced membrane invagination and infection. Nat Cell Biol 12:11–18CrossRefPubMedGoogle Scholar
  19. Feigenson GW (2009) Phase diagrams and lipid domains in multicomponent lipid bilayer mixtures. BiochimBiophysActa 1788:47–52Google Scholar
  20. Frisz JF, Klitzing HA, Lou K, Hutcheon ID, Weber PK, Zimmerberg J, Kraft ML (2013) Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol. J Biol Chem 288:16855–16861CrossRefPubMedPubMedCentralGoogle Scholar
  21. Fujiwara T, Ritchie K, Murakoshi H, Jacobson K, Kusumi A (2002) Phospholipids undergo hop diffusion in compartmentalized cell membrane. J Cell Biol 157:1071–1081CrossRefPubMedPubMedCentralGoogle Scholar
  22. García-Sáez AJ, Schwille P (2010) Stability of lipid domains. FEBS Lett 584:1653–1658CrossRefPubMedGoogle Scholar
  23. Garcia-Saez AJ, Chiantia S, Schwille P (2007) Effect of line tension on the lateral organization of lipid membranes. J Biol Chem 282:33537–33544CrossRefPubMedGoogle Scholar
  24. Gennis RB (1989) Biomembranes: molecular structure and function. Springer, New YorkCrossRefGoogle Scholar
  25. Harris J, Werling D, Hope JC, Taylor G, Howard CJ (2002) Caveolae and caveolin in immune cells: distribution and functions. Trends Immunol 23:158–164CrossRefPubMedGoogle Scholar
  26. Heerklotz H (2002) Triton promotes domain formation in lipid raft mixtures. Biophys J 83:2693–2701CrossRefPubMedPubMedCentralGoogle Scholar
  27. Heinrich M, Tian A, Esposito C, Baumgart T (2009) Dynamic sorting of lipids and proteins in membrane tubes with a moving phase boundary. Proc Natl Acad Sci U S A 107:7208–7213CrossRefGoogle Scholar
  28. Honerkamp-Smith AR, Veatch SL, Keller SL (2009) An introduction to critical points for biophysicists; observations of compositional heterogeneity in lipid membranes. Biochim Biophys Acta 1788:53–63CrossRefPubMedGoogle Scholar
  29. Ipsen JH, Karlström G, Mouritsen OG, Wennerström H, Zuckermann MJ (1987) Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim Biophys Acta 905:162–172CrossRefPubMedGoogle Scholar
  30. Ipsen JH, Mouritsen OG, Zuckermann MJ (1989) Theory of thermal anomalies in the specific heat of lipid bilayers containing cholesterol. Biophys J 56:661–667CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kajiwara K, Watanabe R, Pichler H, Ihara K, Murakami S, Riezman H, Funato K (2008) Yeast ARV1 is required for efficient delivery of an early GPI intermediate to the first mannosyltransferase during DPI assembly and controls lipid flow from the endoplasmic reticulum. Mol Biol Cell 19:2069–2082CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kiessling V, Crane JM, Tamm LK (2006) Transbilayer effects of raft-like lipid domains in asymmetric planar bilayers measured by single molecule tracking. Biophys J 91:3313–3326CrossRefPubMedPubMedCentralGoogle Scholar
  33. Klemm RW, Ejsing CS, Surma MA, Kaiser HJ, Gerl MJ, Sampaio JL, de Robillard Q, Ferguson C, Proszynski TJ, Shevchenko A, Simons K (2009) Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network. J Cell Biol 185:601–612CrossRefPubMedPubMedCentralGoogle Scholar
  34. Lehtonen JY, Holopainen JM, Kinnunen PK (1996) Evidence for the formation of microdomains in liquid crystalline large unilamellar vesicles caused by hydrophobic mismatch of the constituent phospholipids. Biophys J 70:1753–1760CrossRefPubMedPubMedCentralGoogle Scholar
  35. Li H, Papadopoulos V (1998) Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology 139:4991–4997CrossRefPubMedGoogle Scholar
  36. Lipowsky R (1992) Budding of membranes induced by intramembrane domains. J de Physique II 2:1825–1840CrossRefGoogle Scholar
  37. Lopez D, Koch G (2017) Exploring functional membrane microdomains in bacteria: an overview. Curr Opin Microbiol 36:76–84CrossRefPubMedPubMedCentralGoogle Scholar
  38. Lorizate M, Sachsenheimer T, Glass B, Habermann A, Gerl MJ, Kräusslich HG, Brügger B (2013) Comparative lipidomics analysis of HIV-1 particles and their producer cell membrane in different cell lines. Cell Microbiol 15:292–304CrossRefGoogle Scholar
  39. Makushok T, Alves P, Huisman SM, Kijowski AR, Brunner D (2016) Sterol-rich membrane domains define fission yeast cell polarity. Cell 165:1182–1196CrossRefPubMedGoogle Scholar
  40. McLaughlin S, Murray D (2005) Plasma membrane phosphoinositide organization by protein electrostatics. Nature 438:605–611CrossRefPubMedGoogle Scholar
  41. Mileykovskaya E, Dowhan W (2009) Cardiolipin membrane domains in prokaryotes and eukaryotes. Biochim Biophys Acta 1788:2084–2091CrossRefPubMedPubMedCentralGoogle Scholar
  42. Mileykovskaya E, Penczek PA, Fang J, Mallampalli VK, Sparagna GC, Dowhan W (2012) Arrangement of the respiratory chain complexes in Saccharomyces cerevisiae supercomplex III2IV2 revealed by single particle cryo-electron microscopy. J Biol Chem 287:23095–23103CrossRefPubMedPubMedCentralGoogle Scholar
  43. Morein S, Killian JA, Sperotto MM (2002) Characterization of the thermotropic behavior and lateral organization of lipid-peptide mixtures by a combined experimental and theoretical approach: effects of hydrophobic mismatch and role of flanking residues. Biophys J 82:1405–1417CrossRefPubMedPubMedCentralGoogle Scholar
  44. Muchova K, Jamroskovic J, Bara’k I (2010) Lipid domains in Bacillus subtilis anucleate cells. Res Microbiol 161:783–790CrossRefPubMedGoogle Scholar
  45. Nakada C, Ritchie K, Oba Y, Nakamura M, Hotta Y, Iino R, Kasai RS, Yamaguchi K, Fujiwara T, Kusumi A (2003) Accumulation of anchored proteins forms membrane diffusion barriers during neuronal polarization. Nat Cell Biol 5:626–632CrossRefPubMedGoogle Scholar
  46. Nickels JD, Cheng X, Mostofian B, Stanley C, Lindner B, Heberle FA, Perticaroli S, Feygenson M, Egami T, Standaert RF, Smith JC, Myles DAA, Ohl M, Katsaras J (2015) Mechanical properties of nanoscopic lipid domains. J Am Chem Soc 137:15772–15780CrossRefPubMedGoogle Scholar
  47. Nickels JD, Chatterjee S, Stanley CB, Qian S, Cheng X, Myles DAA, Standaert RF, Elkins JG, Katsaras J (2017) The in vivo structure of biological membranes and evidence for lipid domains. PLoS Biol 15:e2002214CrossRefPubMedPubMedCentralGoogle Scholar
  48. Nicolson GL (2014) The fluid-mosaic model of membrane structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. BBA-Biomembranes 1838:1451–1466CrossRefPubMedGoogle Scholar
  49. Paila YD, Tiwari S, Chattopadhyay A (2009) Are specific nonannular cholesterol binding sites present in G-protein coupled receptors? Biochim Biophys Acta 1788:295–302CrossRefPubMedGoogle Scholar
  50. Parat M (2009) Chapter 4 The biology of caveolae. Achievements and perspectives. Int Rev Cell Mol Biol 273:117–162CrossRefPubMedGoogle Scholar
  51. Parton RG, Simons K (2007) The multiple faces of caveolae. Nat Rev Mol Cell Biol 8:185–194CrossRefGoogle Scholar
  52. Poveda JA, Fernandez AM, Encinar JA, Gonzalez-Ros JM (2008) Protein-promoted membrane domains. Biochim Biophys Acta 1778:1583–1590CrossRefPubMedGoogle Scholar
  53. Razani B, Woodman SE, Lisanti MP (2002) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54:431–467CrossRefGoogle Scholar
  54. Risbo J, Sperotto MM, Mouritsen OG (1995) Theory of phase equilibria and critical mixing points in binary lipid bilayers. J Chem Phys 103:3643–3656CrossRefGoogle Scholar
  55. Romer W, Berland L, Chambon V, Gaus K, Windschiegl B, Tenza D, Aly MR, Fraisier V, Florent JC, Perrais D, Lamaze C, Raposo G, Steinem C, Sens P, Bassereau P, Johannes L (2007) Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature 450:670–675CrossRefPubMedGoogle Scholar
  56. Ryba NJP, Marsh D (1992) Protein rotational diffusion and lipid/protein interactions in recombinants of bovine rhodopsin with saturated diacylphosphatidylcholines of different chain lengths studied by conventional and saturation transfer electron spin resonance. Biochemistry 31:7511–7518CrossRefPubMedGoogle Scholar
  57. Saenz JP, Grosser D, Bradley AS, Lagny TJ, Lavrynenko O, Broda M, Simons K (2015) Hopanoids as functional analogues of cholesterol in bacterial membranes. Proc Natl Acad Sci U S A 112:11971–11976CrossRefPubMedPubMedCentralGoogle Scholar
  58. Schafer LV, Marrink SJ (2010) Partitioning of lipids at domain boundaries in model membranes. Biophys J 99:L91–L93CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sezgin E, Levental I, Mayor S, Eggeling C (2017) The mystery of membrane organization: composition, regulation and roles of lipid rafts. Nat Rev Mol Cell Biol 18:361–374CrossRefPubMedPubMedCentralGoogle Scholar
  60. Sharma P, Varma R, Sarasij RC, Ira GK, Krishnamoorthy G, Rao M, Mayor S (2004) Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell 116:577–589CrossRefPubMedGoogle Scholar
  61. Simons K, Gerl MJ (2010) Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol 11:688–699CrossRefPubMedGoogle Scholar
  62. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572CrossRefGoogle Scholar
  63. Simons K, Vaz WC (2004) Model systems, lipid rafts, and cell membranes. Annu Rev Biophys BiomolStruct 33:269–295CrossRefGoogle Scholar
  64. Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175:720–731CrossRefPubMedGoogle Scholar
  65. Sorice M, Manganelli V, Matarrese P, Tinari A, Misasi R, Malorni W, Garofalo T (2009) Cardiolipin-enriched raft-like microdomains are essential activating platforms for apoptotic signals on mitochondria. FEBS Lett 583:2447–2450CrossRefGoogle Scholar
  66. Sorre B, Callan-Jonas A, Manneville JB, Nassoy P, Joanny JF, Prost J, Goud B, Bassereau P (2009) Curvature-driven lipid sorting needs proximity to a demixing point and is aided by proteins. Proc Natl Acad Sci U S A 106:5622–5626CrossRefPubMedPubMedCentralGoogle Scholar
  67. Stottrup BL, Veatch SL, Keller SL (2004) Nonequilibrium behavior in supported lipid membranes containing cholesterol. Biophys J 86:2942–2950CrossRefPubMedPubMedCentralGoogle Scholar
  68. Turner MS, Sens P, Socci ND (2005) Nonequilibrium raft like membrane domains under continuous recycling. Phys Rev Lett 95:e168301Google Scholar
  69. van Meer G, Stelzer EH, Wijnaendts-van-Resandt RW, Simons K (1987) Sorting of sphingolipids in epithelial (Madin-Darby canine kidney) cells. J Cell Biol 105:1623–1625CrossRefPubMedGoogle Scholar
  70. van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124CrossRefPubMedPubMedCentralGoogle Scholar
  71. Wallimann T, Tokarska-Schlattner M, Neumann D, Epand RM, Epand RF, Andres RH, Widmer HR, Hornemann T, Saks V, Agarkova I, Schlattner U (2007) Chapter 7 The phosphocreatine circuit. In: Saks V (ed) Molecular systems bioenergetics: energy for life. Wiley, London, pp 195–264CrossRefGoogle Scholar
  72. Watanabe R, Funato K, Venkataraman K, Futerman AH, Riezman H (2002) Sphingolipids are required for the stable membrane association of glycosylphosphatidylinositol-anchored proteins in yest. J Biol Chem 277:49538–49544CrossRefPubMedGoogle Scholar
  73. Webb RJ, East JM, Sharma RP, Lee AG (1998) Hydrophobic mismatch and the incorporation of peptides into lipid bilayers: a possible mechanism for retention in the Golgi. Biochemistry 37:673–679CrossRefPubMedGoogle Scholar
  74. Xu Y, Phoon CK, Berno B, D'Souza K, Hoedt E, Zhang G, Neubert TA, Epand RM, Ren M, Schlame M (2016) Loss of protein association causes cardiolipin degradation in Barth syndrome. Nat Chem Biol 12:641–647CrossRefPubMedPubMedCentralGoogle Scholar
  75. Yang ST, Kiessling V, Simmons JA, White JM, Tamm LK (2015) HIV gp41-mediated membrane fusion occurs at edges of cholesterol-rich lipid domains. Nat Chem Biol 11:424–431CrossRefPubMedPubMedCentralGoogle Scholar
  76. Yethiraj A, Weisshaar JC (2007) Why are lipid rafts not observed in vivo? Biophys J 93:3113–3119CrossRefPubMedPubMedCentralGoogle Scholar
  77. Zech T, Ejsing CS, Gaus K, De Wet B, Shevchenko A, Simons K, Harder T (2009) Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling. EMBO J 28:466–476CrossRefPubMedPubMedCentralGoogle Scholar
  78. Zhang M, Mileykovskaya E, Dowhan W (2002) Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane. J Biol Chem 277:43553–43556CrossRefPubMedGoogle Scholar

Copyright information

© European Biophysical Societies' Association (EBSA) 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Biomedical SciencesMcMaster University, Health Sciences CentreHamiltonCanada

Section editors and affiliations

  • John M. Seddon
    • 1
  1. 1.Membrane Biophysics Platform, Department of Chemistry and Institute of Chemical BiologyImperial College LondonLondonUK