Skip to main content

Theories of Equilibrium Inhomogeneous Fluids

  • Chapter
  • First Online:
Physics of Biological Membranes

Abstract

I review two theoretical explanations for the existence of inhomogeneities in a fluid bilayer, such as the mammalian plasma membrane, which one might well expect to be homogeneous. The first is the existence of a phase separation. If biologically relevant temperatures are below the critical temperature of the separation, then these inhomogeneities are simply inclusions of one phase within the other. One has to understand, however, why macroscopic separation is not seen in the plasma membrane. If biologically relevant temperatures are above the critical temperature, then the inhomogeneities could be ascribed to critical fluctuations. There are difficulties with this interpretation which I note. The second possible interpretation is that the dynamic heterogeneities are evidence of a two-dimensional microemulsion. Several mechanisms which could give rise to it are discussed. Particular attention is paid to the coupling of membrane height fluctuations to composition differences. Such a mechanism naturally gives rise to a length scale which is of the correct order of magnitude for the domains postulated to exist in the plasma membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    Article  CAS  Google Scholar 

  2. Brown D, London E (1998) Structure and origin of ordered lipid domains in biological membranes. J Membr Biol 164:103–114

    Article  CAS  Google Scholar 

  3. Toulmay A, Prinz W (2013) Direct imaging reveals stable micrometer-scale lipid domains that segregate proteins in live cells. J Cell Biol 202:35–44

    Article  CAS  Google Scholar 

  4. Elliott R, Katsov K, Schick M, Szleifer I (2005) Phase separation of saturated and mono-unsaturated lipids as determined from a microscopic model. J Chem Phys 122:044904-1–044904-11

    Article  CAS  Google Scholar 

  5. Shimshick E, McConnell HM (1973) Lateral phase separation in phospholipid membranes. Biochemistry 12:2351–2360

    Article  CAS  Google Scholar 

  6. Ipsen JH, Karlstrom G, Mouritsen O, Wennerstrom H, Zuckermann M (1987) Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim Biophys Acta 905:162–172

    Article  CAS  Google Scholar 

  7. Veatch S, Keller S (2005) Miscibility phase diagrams of giant vesicles containing sphingomyelin. Phys Rev Lett 94:148101-1–148101-4

    Google Scholar 

  8. Elliott R, Szleifer I, Schick M (2006) Phase diagram of a ternary mixture of cholesterol and saturated and unsaturated lipids calculated from a microscopic model. Phys Rev Lett 96:098101-1–098101-4

    Google Scholar 

  9. Putzel GG, Schick M (2008) Phenomenological model and phase behavior of saturated and unsaturated lipids and cholesterol. Biophys J 95:4756–4762

    Article  CAS  Google Scholar 

  10. Putzel G, Schick M (2011) Insights on raft behavior from minimal phenomenological models. J Phys Condens Matter 23:284101:1–284101:5

    Google Scholar 

  11. Risselada H, Marrink S (2008) The molecular face of lipid rafts in model membranes. Proc Natl Acad Sci U S A 105:17367–17372

    Article  CAS  Google Scholar 

  12. Perlmutter JD, Sachs JN (2011) Interleaflet interaction and asymmetry in phase separated lipid bilayers: molecular dynamics simulations. J Am Chem Soc 133:6563–6577

    Article  CAS  Google Scholar 

  13. Onsager L (1944) Crystal statistics. I. A two-dimensional model with and order-disorder transition. Phys Rev 65:117–149

    Article  CAS  Google Scholar 

  14. Honerkamp-Smith AR, Cicuta P, Collins MD, Veatch SL, Schick M, den Nijs MPM, Keller SL (2008) Line tensions, correlation lengths, and critical exponents in lipid membranes near critical points. Biophys J 95:236–246

    Article  CAS  Google Scholar 

  15. Kusumi A, Sako Y, Yamamoto M (1993) Confined lateral diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium-induced differentiation in cultured epithelial cells. Biophys J 65:2021–2040

    Article  CAS  Google Scholar 

  16. Yethiraj A, Weisshaar J (2007) Why are lipid rafts not observed in vivo? Biophys J 93:3113–3119

    Article  CAS  Google Scholar 

  17. Grinstein G, Ma SK (1982) Roughening and lower critical dimension in the random-field ising model. Phys Rev Lett 49:685

    Article  Google Scholar 

  18. Veatch SL, Sengupta P, Honerkamp-Smith A, Holowka D, Baird B (2008) Critical fluctuations in plasma membrane vesicles. ACS Chem Biol 3:287–293

    Article  CAS  Google Scholar 

  19. Matcha B, Veatch S, Sethna J (2012) Critical Casimir forces in cellular membranes. Phys Rev Lett 109:138101

    Article  Google Scholar 

  20. Matcha B, Papanikolaou S, Sethna J, Veatch S (2011) Minimal model of plasma membrane heterogeneity requires coupling cortical actin to criticality. Biophys J 100:1668–1677

    Article  Google Scholar 

  21. Wang TY, Leventis R, Silvius JR (2000) Fluorescence-based evaluation of the partitioning of lipids and lipidated peptides into liquid-ordered microdomains: a model for molecular partitioning into ‘lipid rafts’. Biophys J 79:919–933

    Article  CAS  Google Scholar 

  22. 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 91:3313–3326

    Article  CAS  Google Scholar 

  23. Collins M, Keller S (2008) Tuning lipid mixtures to induce domains across leaflets of unsupported asymmetric bilayers. Proc Natl Acad Sci U S A 105:124–128

    Article  CAS  Google Scholar 

  24. Putzel G, Schick M (2008) Phase behavior of a model bilayer membrane with coupled leaves. Biophys J 94:869–877

    Article  CAS  Google Scholar 

  25. Wagner AJ, Loew S, May S (2007) Influence of monolayer-monolayer coupling on the phase behavior of a fluid lipid bilayer. Biophys J 93:4268–4277

    Article  CAS  Google Scholar 

  26. Ingólfsson H, Melo M, van Eerden F, Amarez C, Lopez CA, Wassenaar TA, Periole X, de Vries AH, Tieleman DP, Marrink SJ (2014) Lipid organization of the plasma membrane. J Am Chem Soc 136:14554–14559

    Article  Google Scholar 

  27. Gompper G, Schick M (1994) Self-assembling amphiphilic systems. Academic, San Diego

    Google Scholar 

  28. Prigogine I, Defay R (1954) Chemical thermodynamics. Longmans Green, London

    Google Scholar 

  29. Konyakhina T, Goh S, Amazon J, Heberle F, Wu J, Feigenson G (2011) Control of a nanoscopic-to-macroscopic transition:modulated phases in four-component DSPC/DOPC/POPC/Chol giant unilamellar vesicles. Biophys J 101:L08–L10

    Article  Google Scholar 

  30. Goh SL, Amazon J, Feigenson G (2013) Toward a better raft model: modulated phases in the four-component bilayer, DSPC/DOPC/POPC/Chol. Biophys J 104:853–862

    Article  CAS  Google Scholar 

  31. Stanich CA, Honerkamp-Smith AR, Putzel GG, Warth CS, Lamprecht AK, Mandal P, Mann E, Hua T-AD, Keller SL (2013) Coarsening dynamics of domains in lipid membranes. Biophys J 106:444–454

    Article  Google Scholar 

  32. Veatch SL, Gawrisch K, Keller SL (2006) Closed-loop miscibility gap and quantitative tie-lines in ternary membranes containing diphytanoyl PC. Biophys J 90:4428–4436

    Article  CAS  Google Scholar 

  33. Yamamoto T, Brewster R, Safran S (2010) Chain ordering of hybrid lipids can stabilize domains in saturated/hybrid/cholesterol lipid membranes. Euro Phys Lett 91:28002:1–28002:6

    Article  Google Scholar 

  34. Palmieri B, Safran S (2013) Hybrid lipids increase the probability of fluctuating nanodomains in mixed membranes. Langmuir 29:5246–5261

    Article  CAS  Google Scholar 

  35. Matsen M, Sullivan D (1992) Lattice model for microemulsions in two dimensions. Phys Rev A 46:1985–1991

    Article  CAS  Google Scholar 

  36. Hirose Y, Komura S, Andelman DA (2009) Coupled modulated bilayers: a phenomenological model. ChemPhysChem 10:2839–2846

    Article  CAS  Google Scholar 

  37. Hirose Y, Komura S, Andelman D (2012) Concentration fluctuations and phase transitions in coupled modulated bilayers. Phys Rev E 86:021916-1–021916-113

    Google Scholar 

  38. Palmieri B, Yamamoto T, Brewster R, Safran S (2014) Line active molecules promote inhomogeneous structures in membranes: theory, simulations and experiments. Adv Colloid Interf Sci 208:58–65

    Article  CAS  Google Scholar 

  39. Komura S, Andelman D (2014) Physical aspects of heterogeneities in multi-component lipid membranes. Adv Colloid Interf Sci 208:34–46

    Article  CAS  Google Scholar 

  40. Heberle F, Doctorova M, Goh S, Standaert RS, Katsaras J, Feigenson GW (2013) Hybrid and nonhybrid lipids exert common effects on membrane raft size and morphology. J Am Chem Soc 135:14932–14935

    Article  CAS  Google Scholar 

  41. Seul M, Andelman D (1995) Domain shapes and patterns; the phenomenology of modulated phases. Science 267:476–483

    Article  CAS  Google Scholar 

  42. Leibler S (1986) Curvature instability in membranes. J Phys 47:507–516

    Article  CAS  Google Scholar 

  43. Leibler S, Andelman D (1987) Ordered and curved meso-structures in membranes and amphiphilic films. J Phys 48:2013–2018

    Article  CAS  Google Scholar 

  44. Vidal IB, Rosetti CM, Pastorino C, Müller M (2014) Measuring the composition-curvature coupling in binary lipid membranes by computer simulation. J Chem Phys 141:194902

    Article  Google Scholar 

  45. Kumar PBS, Gompper G, Lipowsky R (1999) Modulated phases in multicomponent fluid membranes. Phys Rev E 60:4610–4618

    Article  CAS  Google Scholar 

  46. Schick M (2012) Membrane heterogeneity: manifestation of a curvature-induced microemulsion. Phys Rev E 85:031902-1–031902-4

    Google Scholar 

  47. Kollmitzer B, Heftberger P, Rappolt M, Pabst G (2013) Monolayer spontaneous curvature of raft-forming membrane lipids. Soft Matter 9:10877–10884

    Article  CAS  Google Scholar 

  48. Shlomovitz R, Schick M (2013) Model of a raft in both leaves of an asymmetric lipid bilayer. Biophys J 105:1406–1413

    Article  CAS  Google Scholar 

  49. Safran S (1994) Statistical thermodynamics of surfaces, interfaces, and membranes. Addison-Wesley, Reading

    Google Scholar 

  50. Diamant H (2011) Model-free thermodynamics of fluid vesicles. Phys Rev E 84:061123-1–061123-7

    Google Scholar 

  51. Farago O, Pincus P (2004) Statistical mechanics of bilayer membrane with a fixed projected area. J Chem Phys 120:2934–2950

    Article  CAS  Google Scholar 

  52. Meinhardt S, Vink R, Schmid F (2013) Monolayer curvature stabilizes nanoscale raft domains in mixed lipid bilayers. Proc Natl Acad Sci U S A 110:4476–4481

    Article  CAS  Google Scholar 

  53. Brodbek L, Schmid F (2016) Interplay of curvature-induced micro- and nanodomain structures in multicomponent lipid bilayers. Int J Adv Eng Sci Appl Math 8:111–120

    Article  Google Scholar 

  54. Liu J, Qi S, Groves J, Chakraborty A (2005) Phase segregation on different length scales in a model cell membrane system. J Phys Chem 109:19960–19969

    Article  CAS  Google Scholar 

  55. Gompper G, Schick M (1990) Lattice model of microemulsions. Phys Rev B 41:9148–9162

    Article  CAS  Google Scholar 

  56. Pontes B, Ayala Y, Fonseca A, Romao L, Amaral R, Salgado L, Lima FR, Farina M, Viana NB, Moura-Neto V, Nussenzveig HM (2013) Membrane elastic properties and cell function. PLOS One 8:67708

    Article  Google Scholar 

  57. Shlomovitz R, Maibaum L, Schick M (2014) Macroscopic phase separation, modulated phases, and microemulsions: a unified picture of rafts. Biophys J 106:1979–1985

    Article  CAS  Google Scholar 

  58. Sadeghi S, Müller M, Vink RL (2014) Raft formation in lipid bilayers coupled to curvature. Biophys J 107:1591–1600

    Article  CAS  Google Scholar 

  59. Gompper G, Schick M (1990) Lattice model of microemulsions: the effect of fluctuations in one and two dimensions. Phys Rev A 42:2137–2149

    Article  CAS  Google Scholar 

  60. Heberle F, Petruzielo R, Pan J, Drazba P, Kucerka N, Standaert R, Feigenson GW, Katsaras J (2013) Bilayer thickness mismatch controls domain size in model membranes. J Am Chem Soc 135:6853–6859

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I have been working in this area for many years now and have been fortunate in my colleagues. First and foremost are the “amphiphilophiles” with whom I meet weekly: Sarah Keller, Lutz Maibaum, and their students, both current and former, like Sarah Veatch, Aurelia Honerkamp Smith, and Matt Blosser, and Post-Doctoral Fellows, Marcus Collins and Thomas Portet. I thank my own Post-Doctoral Fellows, Roie Shlomovitz and Ha Giang for many hours of stimulating conversation. I have enjoyed interactions on the theory of this subject with former colleagues, Marcus Mueller and Friederike Schmid, and am grateful to the experimentalists who have shared their knowledge with me: Erwin London, Gerry Feigenson, and John Katsaras. Finally I am indebted to the National Science Foundation for their constant support. This work was supported by the NSF on Grant No. DMR-1203282.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Schick .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Schick, M. (2018). Theories of Equilibrium Inhomogeneous Fluids. In: Bassereau, P., Sens, P. (eds) Physics of Biological Membranes. Springer, Cham. https://doi.org/10.1007/978-3-030-00630-3_5

Download citation

Publish with us

Policies and ethics