Adhesion of Biological Membranes

  • Kheya Sengupta
  • Ana-Sunčana SmithEmail author


One of the most important triggers of cell activity is adhesion, a process by which cells and their organelles interact and attach to substrates, internal scaffolds, external interfaces, or other cells. The physiological and pathological significance of cell adhesion is hard to exaggerate, and adhesion is ubiquitous in the living world. Adhesive contacts need to be able to function in widely varying circumstances and must be established in an extremely noisy environment. For these reasons, the control mechanisms of adhesion have had to develop so as to be able to permanently monitor and correct cellular performance. While a lot of effort has been invested into understanding the biochemical aspect of these processes, the underlying physical principles of adhesion regulation have obtained significantly less appreciation. Only in recent years have these two approaches begun to converge in a unified view. Due to the strong coupling of the biochemical reactions to the spatial coordination provided by membranes and the cytoskeleton, biological signaling is subject to a plethora of physical constraints. Indeed, many signaling pathways, particularly those involving the adhesion, involve protein diffusion and aggregation guided by membranes. It is these aspects of adhesion that can be understood in the framework of statistical physics, as we intend to demonstrate in this short review. Here we summarize the developments in understanding cell and membrane adhesion from a theoretical point of view and support it with experiments in model systems as well as with living cells.


Cell adhesion Artificial cell Ligand–receptor interactions Competitive binding Multiscale approaches to adhesion 



We are grateful to our mentors Erich Sackmann, Udo Seifert, and Rudolf Merkel for their insights and ongoing collaborations. We are thankful to our teams and colleagues who were instrumental in realizing the work summarized herein, especially Susanne Fenz, Cornelia Monzel, Daniel Smith, Timo Bihr, and Laurent Limozin. We thank Josip Augustin Janeš for the help with formatting and proofreading this chapter.


  1. 1.
    Smith A-S, Fenz SF, Sengupta K (2010) Inferring spatial organization of bonds within adhesion clusters by exploiting fluctuations of soft interfaces. EPL 89:28003:1–6Google Scholar
  2. 2.
    Kaliman S, Jayachandran C, Rehfeldt F, Smith A-S (2014) Novel growth regime of MDCK II model tissues on soft substrates. Biophys J 106(7):L25–L28PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular biology of the cell. Garland Science, New York, 1392 ppGoogle Scholar
  4. 4.
    Lipowsky R (1995) Generic interactions of flexible membranes. In: Lipowsky R, Sackmann, E (eds) Structure and dynamics of membranes, Chapter 11. Elsevier, Amsterdam, pp 521–602Google Scholar
  5. 5.
    Smith A-S, Sackmann E (2009) Progress in mimetic studies of cell adhesion and the mechanosensing. ChemPhysChem 10(1):66–78PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Fenz SF, Sengupta, K (2012) Giant vesicles as cell models. Integr Biol 4(9):982–995CrossRefGoogle Scholar
  7. 7.
    Sackmann E, Smith A-S (2014) Physics of cell adhesion: some lessons from cell-mimetic systems. Soft Matter 10(11):1644–1659PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Fenz SF, Smith A-S, Merkel R, Sengupta K (2011) Inter-membrane adhesion mediated by mobile linkers: effect of receptor shortage. Soft Matter 7(3):952CrossRefGoogle Scholar
  9. 9.
    Bruinsma R, Sackmann E (2001) Bioadhesion and the dewetting transition. C R Acad Sci 2:803–815Google Scholar
  10. 10.
    Prechtel K, Bausch AR, Marchi-Artzner V, Kantlehner M, Kessler H, Merkel R (2002) Dynamic force spectroscopy to probe adhesion strength of living cells. Phys Rev Lett 89(2):028101PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Evans EA (1980) Analysis of adhesion of large vesicles to surfaces. Biophys J 31(3):425PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Steinkühler J, Agudo-Canalejo J, Lipowsky R, Dimova R (2016) Modulating vesicle adhesion by electric fields. Biophys J 111(7):1454–1464PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Limozin L, Sengupta K (2007) Modulation of vesicle adhesion and spreading kinetics by hyaluronan cushions. Biophys J 93(9):3300–3313PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Smith A-S, Lorz BG, Seifert U, Sackmann E (2006) Antagonist-induced deadhesion of specifically adhered vesicles. Biophys J 90:1064–1080PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Rädler JO, Feder TJ, Strey HH, Sackmann E (1995) Fluctuation analysis of tension-controlled undulation forces between giant vesicles and solid substrates. Phys Rev E 51:4526–4536CrossRefGoogle Scholar
  16. 16.
    Limozin L, Sengupta K (2009) Quantitative reflection interference contrast microscopy (RICM) in soft matter and cell adhesion. ChemPhysChem 10(16):2752–2768PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Schilling J, Sengupta K, Goennenwein S, Bausch AR, Sackmann E (2004) Absolute interfacial distance measurements by dual-wavelength reflection interference contrast microscopy. Phys Rev E 69:021901CrossRefGoogle Scholar
  18. 18.
    Monzel C, Fenz SF, Merkel R, Sengupta K (2009) Probing biomembrane dynamics by dual-wavelength reflection interference contrast microscopy. ChemPhysChem 10:2828–2838PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Sengupta K, Limozin L (2010) Adhesion of soft membranes controlled by tension and interfacial polymers. Phys Rev Lett 104(8):088101PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Smith A-S, Sengupta K, Goennenwein S, Seifert U, Sackmann E (2008) Force-induced growth of adhesion domains is controlled by receptor mobility. Proc Natl Acad Sci U S A 105(19):6906–6911PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Rädler JO, Feder TJ, Strey HH, Sackmann E (1995) Fluctuation analysis of tension-controlled undulation forces between giant vesicles and solid substrates. Phys Rev E 51:4526–4536CrossRefGoogle Scholar
  22. 22.
    Sackmann E (1996) Supported membranes: scientific and practical applications. Science 271(5245):43PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Groves JT, Ulman N, Boxer SG (1997) Micropatterning fluid lipid bilayers on solid supports. Science 275(5300):651–653PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Richter RP, Bérat R, Brisson AR (2006) Formation of solid-supported lipid bilayers: an integrated view. Langmuir 22(8):3497–3505PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Elender G, Kühner M, Sackmann E (1996) Functionalisation of si/sio 2 and glass surfaces with ultrathin dextran films and deposition of lipid bilayers. Biosens Bioelectron 11(6):565–577PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Fischlechner M, Zaulig M, Meyer S, Estrela-Lopis I, Cuéllar L, Irigoyen J, Pescador P, Brumen M, Messner P, Moya S, et al (2008) Lipid layers on polyelectrolyte multilayer supports. Soft Matter 4(11):2245–2258CrossRefGoogle Scholar
  27. 27.
    Mulligan K, Jakubek ZJ, Linda JJ (2011) Supported lipid bilayers on biocompatible polysaccharide multilayers. Langmuir 27(23):14352–14359PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Wagner ML, Tamm LK (2000) Tethered polymer-supported planar lipid bilayers for reconstitution of integral membrane proteins: silane-polyethyleneglycol-lipid as a cushion and covalent linker. Biophys J 79(3):1400–1414PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Naumann CA, Prucker O, Lehmann T, Rühe J, Knoll W, Frank CW (2002) The polymer-supported phospholipid bilayer: tethering as a new approach to substrate-membrane stabilization. Biomacromolecules 3(1):27–35PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Tanaka M, Sackmann E (2005) Polymer-supported membranes as models of the cell surface. Nature 437(7059):656–663PubMedCrossRefGoogle Scholar
  31. 31.
    Ada Cavalcanti-Adam E, Volberg T, Micoulet A, Kessler H, Geiger B, Spatz JP (2007) Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys J 92(8):2964–2974CrossRefGoogle Scholar
  32. 32.
    Spatz JP, Geiger B (2007) Molecular engineering of cellular environments: cell adhesion to nano-digital surfaces. Methods Cell Biol 83:89–111PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Pi F, Dillard P, Alameddine R, Benard E, Wahl A, Ozerov I, Charrier A, Limozin L, Sengupta K (2015) Size-tunable organic nanodot arrays: a versatile platform for manipulating and imaging cells. Nano Lett 15(8):5178–5184. PMID: 26161675PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Dillard P, Pi F, Lellouch AC, Limozin L, Sengupta K (2016) Nano-clustering of ligands on surrogate antigen presenting cells modulates t cell membrane adhesion and organization. Integr Biol 8(3):287–301CrossRefGoogle Scholar
  35. 35.
    Mossman KD, Campi G, Groves JT, Dustin ML (2005) Altered TCR signaling from geometrically repatterned immunological synapses. Science 310(5751):1191–1193PubMedCrossRefGoogle Scholar
  36. 36.
    Hartman NC, Nyeb JA, Groves JT (2009) Cluster size regulates protein sorting in the immunological synapse. Proc Natl Acad Sci U S A 106:12729–12734PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Fenz S, Bihr T, Schmidt D, Merkel R, Seifert U, Sengupta K, Smith A-S (2017) Membrane fluctuations mediate lateral interactions between cadherin bonds. Nat Phys 13:906–913CrossRefGoogle Scholar
  38. 38.
    Lodish H, Zipursky SL (2001) Molecular cell biology. Biochem Mol Biol Educ 29:126–133Google Scholar
  39. 39.
    Janeway C, Murphy KP, Travers P, Walport M (2008) Janeway’s immunobiology. Garland Science, New YorkGoogle Scholar
  40. 40.
    Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Kim M, Carman CV, Springer TA (2003) Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301(5640):1720–1725PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Bershadsky A, Kozlov M, Geiger B (2006) Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. Curr Opin Cell Biol 18:472–481PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Vogel V, Sheetz M (2006) Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol 7(4):265–275PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Geiger B, Yamada KM (2011) Molecular architecture and function of matrix adhesions. Cold Spring Harb Perspect Biol 3(5):a005033PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Iskratsch T, Wolfenson H, Sheetz MP (2014) Appreciating force and shape the rise of mechanotransduction in cell biology. Nat Rev Mol Cell Biol 15(12):825–833PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Solon J, Levental I, Sengupta K, Georges PC, Janmey PA (2007) Fibroblast adaptation and stiffness matching to soft elastic substrates. Biophys J 93(12):4453–4461PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Merkel R, Nassoy P, Leung A, Ritchie K, Evans E (1999) Energy landscapes of receptor–ligand bonds explored with dynamic force spectroscopy. Nature 397(6714):50–53PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Evans EA, Calderwood DA (2007) Forces and bond dynamics in cell adhesion. Science 316(5828):1148–1153PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Dembo M, Torney DC, Saxman K, Hammer D (1988) The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proc R Soc Lond B Biol Sci 234(1274):55–83PubMedPubMedCentralGoogle Scholar
  50. 50.
    Kong F, García AJ, Paul Mould A, Humphries MJ, Zhu C (2009) Demonstration of catch bonds between an integrin and its ligand. J Cell Biol 185(7):1275–1284PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Leckband DE, de Rooij J (2014) Cadherin adhesion and mechanotransduction. Annu Rev Cell Dev Biol 30:291–315PubMedCrossRefGoogle Scholar
  52. 52.
    Lecuit T, Yap AS (2012) E-cadherin junctions as active mechanical integrators in tissue dynamics. Nat Cell Biol 17(5):533–539CrossRefGoogle Scholar
  53. 53.
    Volk T, Cohen O, Geiger B (1987) Formation of heterotypic adherens-type junctions between l-cam-containing liver cells and a-cam-containing lens cells. Cell 50(6):987–994PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Ayalon O, Sabanai H, Lampugnani MG, Dejana E, Geiger B (1994) Spatial and temporal relationships between cadherins and pecam-1 in cell-cell junctions of human endothelial cells. J Cell Biol 126(1):247–258PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Engl W, Arasi B, Yap LL, Thiery JP, Viasnoff V (2014) Actin dynamics modulate mechanosensitive immobilization of E-cadherin at adherens junctions. Nat Cell Biol 16(6):587–594PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Gumbiner BM (2005) Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 6(8):622–634PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Jeanes A, Gottardi CJ, Yap AS (2008) Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27(55):6920–6929PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Bello SM, Millo H, Rajebhosale M, Price SR (2012) Catenin-dependent cadherin function drives divisional segregation of spinal motor neurons. J Neurosci 32(2):490–505PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Katsamba P, Carroll K, Ahlsen G, Bahna F, Vendome J, Posy S, Rajebhosale M, Price S, Jessell TM, Ben-Shaul A, Shapiro L, Honig BH (2009) Linking molecular affinity and cellular specificity in cadherin-mediated adhesion. Proc Natl Acad Sci U S A 106(28):11594–11599PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Wu Y, Vendome J, Shapiro L, Ben-Shaul A, Honig B (2011) Transforming binding affinities from three dimensions to two with application to cadherin clustering. Nature 475(7357):510–513PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Hong S, Troyanovsky RB, Troyanovsky SM (2010) Spontaneous assembly and active disassembly balance adherens junction homeostasis. Proc Natl Acad Sci U S A 107(8):3528–3533PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Taveau J-C, Dubois M, Le Bihan O, Trépout S, Almagro S, Hewat E, Durmort C, Heyraud S, Gulino-Debrac D, Lambert O (2008) Structure of artificial and natural ve-cadherinbased adherens junctions. Biochem Soc Trans 36(2):189–193PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Ozaki C, Obata S, Yamanaka H, Tominaga S, Suzuki ST (2010) The extracellular domains of e- and n-cadherin determine the scattered punctate localization in epithelial cells and the cytoplasmic domains modulate the localization. J Biochem 147(3):415PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Harrison OJ, Jin X, Hong S, Bahna F, Ahlsen G, Brasch J, Wu Y, Vendome J, Felsovalyi K, Hampton CM, Troyanovsky RB, Ben-Shaul A, Frank J, Troyanovsky SM, Shapiro L, Honig B (2011) The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins. Structure 19(2):244–256PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Hong S, Troyanovsky RB, Troyanovsky SM (2013) Binding to f-actin guides cadherin cluster assembly, stability, and movement. J Cell Biol 201(1):131–143PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Biswas KH, Hartman KL, Yu C, Harrison OJ, Song H, Smith AW, Huang WYC, Lin W, Guo Z, Padmanabhan A, Troyanovsky SM, Dustin ML, Shapiro L, Honig B, Zaidel-Bara R, Groves JT (2015) E-cadherin junction formation involves an active kinetic nucleation process. Proc Natl Acad Sci U S A 112(35):10932–10937PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Brasch J, Harrison OJ, Honig B, Shapiro L (2012) Thinking outside the cell: how cadherins drive adhesion. Trends Cell Biol 22(6):299–310PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Dustin ML, Groves JT (2012) Receptor signaling clusters in the immune synapse. Ann Rev Biophys 41:543CrossRefGoogle Scholar
  69. 69.
    Varma R, Campi G, Yokosuka T, Saito T, Dustin ML (2006) T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 25:117–127PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Kaizuka Y, Douglass AD, Varma R, Dustin ML, Vale RD (2007) Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in jurkat T cells. Proc Natl Acad Sci U S A 104(51):20296–20301PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (1999) The immunological synapse: a molecular machine controlling t cell activation. Science 285(5425):221–227PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Dillard P, Varma R, Sengupta K, Limozin L (2014) Ligand-mediated friction determines morphodynamics of spreading t cells. Biophys J 107(11):2629–2638PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Bihr T, Seifert U, Smith A-S (2012) Nucleation of ligand-receptor domains in membrane adhesion. Phys Rev Lett 109:258101PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Pincus P, Joanny J-F, Andelman D (1990) Electrostatic interactions, curvature elasticity, and steric repulsion in multimembrane systems. Europhys Lett 11:763CrossRefGoogle Scholar
  75. 75.
    Safinya CR, Roux D, Smith GS, Sinha SK, Dimon P, Clark NA, Bellocq AM (1986) Steric interactions in a model multimembrane system: a synchrotron X-ray study. Phys Rev Lett 57:2718PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Helfrich W (1973) Elastic properties of lipid bilayers: theory and possible experiments. Z Naturforsch C J Biosci 28:693–703CrossRefGoogle Scholar
  77. 77.
    Brochard F, Lennon JF (1975) Frequency spectrum of the flicker phenomenon in erythrocytes. J Phys Fr 36:11Google Scholar
  78. 78.
    Evans E, Rawicz W (1990) Entropy-driven tension and bending elasticity in condensed-fluid membranes. Phys Rev Lett 64:2094–2097PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Zidovska A, Sackmann E (2006) Brownian motion of nucleated cell envelopes impedes adhesion. Phys Rev Lett 96(4):048103PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Pelling AE, Veraitch FS, Chu CP-K, Nicholls BM, Hemsley AL, Mason C, Horton MA (2007) Mapping correlated membrane pulsations and fluctuations in human cells. J Mol Recognit 20:467PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Auth T, Safran SA, Gov NS (2007) Fluctuations of coupled fluid and solid membranes with application to red blood cells. Phys Rev E 76:051910CrossRefGoogle Scholar
  82. 82.
    Pierres A, Benoliel A-M, Touchard D, Bongrand P (2008) How cells tiptoe on adhesive surfaces before sticking. Biophys J 94:4114PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Safran SA, Gov N, Nicolas A, Schwarz US, Tlusty T (2005) Physics of cell elasticity, shape and adhesion. Physica A 352:171CrossRefGoogle Scholar
  84. 84.
    Betz T, Lenz M, Joanny J-F, Sykes C (2009) ATP-dependent mechanics of red blood cells. Proc Natl Acad Sci U S A 106(36):15320–15325PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Loubet B, Seifert U, Lomholt MA (2012) Effective tension and fluctuations in active membranes. Phys Rev E 85:031913CrossRefGoogle Scholar
  86. 86.
    Turlier H, Fedosov DA, Audoly B, Auth T, Gov NS, Sykes C, Joanny J-F, Gompper G, Betz T (2016) Equilibrium physics breakdown reveals the active nature of red blood cell flickering. Nat Phys 12:513–519CrossRefGoogle Scholar
  87. 87.
    Smith A-S (2016) Biophysics: alive and twitching. Nat Phys 12(5):378–379CrossRefGoogle Scholar
  88. 88.
    Monzel C, Schmidt D, Seifert U, Smith A-S, Merkel R, Sengupta K (2016) Nanometric thermal fluctuations of weakly confined biomembranes measured with microsecond time-resolution. Soft Matter 12(21):4755–4768PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Netz RR, Lipowsky R (1995) Stacks of fluid membranes under pressure and tension. Europhys Lett 29:345–350CrossRefGoogle Scholar
  90. 90.
    Monzel C, Fenz SF, Giesen M, Merkel R, Sengupta K (2012) Mapping fluctuations in biomembranes adhered to micropatterns. Soft Matter 8(22):6128CrossRefGoogle Scholar
  91. 91.
    Schmidt D, Monzel C, Bihr T, Merkel R, Seifert U, Sengupta K, Smith A-S (2014) Signature of a nonharmonic potential as revealed from a consistent shape and fluctuation analysis of an adherent membrane. Phys Rev X 4(2):021023Google Scholar
  92. 92.
    Seifert U (1995) Self-consistent theory of bound vesicles. Phys Rev Lett 74:5060–5063PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Mecke KR, Charitat T, Graner F (2003) Fluctuating lipid bilayer in an arbitrary potential: theory and experimental determination of bending rigidity. Langmuir 19:2080–2087CrossRefGoogle Scholar
  94. 94.
    Lipowsky R, Leibler S (1986) Unbinding transitions of interacting membranes. Phys Rev Lett 56:2541–2544PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Netz RR (1995) Complete unbinding of fluid membranes in the presence of short-ranged forces. Phys Rev E 51(3):2286–2294CrossRefGoogle Scholar
  96. 96.
    Hategan A, Sengupta K, Kahn S, Sackmann E, Discher DE (2004) Topographical pattern dynamics in passive adhesion of cell membranes. Biophys J 87(5):3547–3560PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Manghi M, Destainville N (2010) Statistical mechanics and dynamics of two supported stacked lipid bilayers. Langmuir 26:4057–4068PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Bruinsma R, Goulian M, Pincus P (1994) Self-assembly of membrane junctions. Biophys J 67:746–750PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Brown FLH (2008) Elastic modeling of biomembranes and lipid bilayers. Annu Rev Phys Chem 59:685–712PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Speck T (2011) Effective free energy for pinned membranes. Phys Rev E 83:050901CrossRefGoogle Scholar
  101. 101.
    Monzel C, Schmidt D, Kleusch C, Kirchenbüchler D, Seifert U, Smith A-S, Sengupta K, Merkel R (2015) Measuring fast stochastic displacements of bio-membranes with dynamic optical displacement spectroscopy. Nat Commun 6:8162PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Schmidt D, Bihr T, Fenz S, Merkel R, Seifert U, Sengupta K, Smith A-S (2015) Crowding of receptors induces ring-like adhesions in model membranes. Biochim Biophys Acta Mol Cell Res 1853:2984–2991CrossRefGoogle Scholar
  103. 103.
    Smith A-S, Seifert U (2007) Vesicles as a model for controlled (de-)adhesion of cells: a thermodynamic approach. Soft Matter 3:275–289CrossRefGoogle Scholar
  104. 104.
    Lorz BG, Smith A-S, Gege C, Sackmann E (2007) Adhesion of giant vesicles mediated by weak binding of sialyl-LewisX to E-selectin in the presence of repelling poly(ethylene glycol) molecules. Langmuir 23:12293–12300PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Boehm H, Mundinger TA, Boehm CHJ, Hagel V, Rauch U, Spatz JP, Curtis JE (2009) Mapping the mechanics and macromolecular organization of hyaluronan-rich cell coats. Soft Matter 5:4331–4337CrossRefGoogle Scholar
  106. 106.
    McLane LT, Chang P, Granqvist A, Boehm H, Kramer A, Scrimgeour J, Curtis JE (2013) Spatial organization and mechanical properties of the pericellular matrix on chondrocytes. Biophys J 104(5):986–996PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Chang PS, McLane LT, Fogg R, Scrimgeour J, Temenoff JS, Granqvist A, Curtis JE (2016) Cell surface access is modulated by tethered bottlebrush proteoglycans. Biophys J 110(12):2739–2750PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Robert P, Limozin L, Benoliel A-M, Bongrand P (2006) Glycocalyx regulation of cell adhesion. Principles of cellular engineering: understanding the biomolecular interface. Academic, Boston, p 143Google Scholar
  109. 109.
    Marx S, Schilling J, Sackmann E, Bruinsma R (2002) Helfrich repulsion and dynamical phase separation of multicomponent lipid bilayers. Phys Rev Lett 88:138102PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Hisette M-L, Haddad P, Gisler T, Marques CM, Schröder AP (2008) Spreading of bio-adhesive vesicles on DNA carpets. Soft Matter 4(4):828–832CrossRefGoogle Scholar
  111. 111.
    Nam G, Hisette ML, Sun YL, Gisler T, Johner A, Thalmann F, Schröder AP, Marques CM, Lee N-K (2010) Scraping and stapling of end-grafted DNA chains by a bioadhesive spreading vesicle to reveal chain internal friction and topological complexity. Phys Rev Lett 105(8):088101PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Bruinsma R, Behrisch A, Sackmann E (2016) Adhesive switching of membranes: experiment and theory. Phys Rev E 61:4253–4267CrossRefGoogle Scholar
  113. 113.
    Schmid EM, Bakalar MH, Choudhuri K, Weichsel J, Ann HS, Geissler PL, Dustin ML, Fletcher DA (2000) Size-dependent protein segregation at membrane interfaces. Nat Phys 12:704–711CrossRefGoogle Scholar
  114. 114.
    Paszek MJ, DuFort CC, Rossier O, Bainer R, Mouw JK, Godula K, Hudak JE, Lakins JN, Wijekoon AC, Cassereau L, Rubashkin MG, Magbanua MJ, Thorn KS, Davidson MW, Rugo HS, Park JW, Hammer DA, Giannone G, Bertozzi CR, Weaver VM (2014) The cancer glycocalyx mechanically primes integrin-mediated growth and survival. Nature 511:319–325PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Seifert U (1997) Configurations of fluid membranes and vesicles. Adv Phys 46:13–137CrossRefGoogle Scholar
  116. 116.
    Smith A-S, Seifert U (2005) Effective adhesion strength of specifically bound vesicles. Phys Rev E 71:061902CrossRefGoogle Scholar
  117. 117.
    Groves JT (2007) Bending mechanics and molecular organization in biological membranes. Annu Rev Phys Chem 58:697–717PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Brown FLH (2011) Continuumsimulations of biomembrane dynamics and the importance of hydrodynamic effects. Q Rev Biophys 44:391–432PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Schwarz US, Safran SA (2013) Physics of adherent cells. Rev Mod Phys 85:1327–1381CrossRefGoogle Scholar
  120. 120.
    Dustin ML, Chakraborty AK, Shaw AS (2010) Understanding the structure and function of the immunological synapse. Cold Spring Harb Perspect Biol 2(10):a002311PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Bihr T, Fenz S, Sackmann E, Merkel R, Seifert U, Sengupta K, Smith A-S (2014) Association rates of membrane-coupled cell adhesion molecules. Biophys J 107(11):L33–L36PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Döbereiner H-G, Dubin-Thaler BJ, Hofman JM, Xenias HS, Sims TN, Giannone G, Dustin ML, Wiggins CH, Sheetz MP (2006) Lateral membrane waves constitute a universal dynamic pattern of motile cells. Phys Rev Lett 97(3):038102PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Sengupta K, Aranda-Espinoza H, Smith L, Janmey P, Hammer D (2006) Spreading of neutrophils: from activation to migration. Biophys J 91:4638–4648PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Cuvelier D, Théry M, Chu Y-S, Dufour S, Thiéry J-P, Bornens M, Nassoy P, Mahadevan L (2007) The universal dynamics of cell spreading. Curr Biol 17(8):694–699PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Seifert U, Lipowsky R (1990) Adhesion of vesicles. Phys Rev A 42:4768–4771PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Smith A-S, Sackmann E, Seifert U (2004) Pulling tethers from adhered vesicles. Phys Rev Lett 92:208101PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Smith A-S, Sackmann E, Seifert U (2003) Effects of a pulling force on the shape of a bound vesicle. Europhys Lett 64:281–287CrossRefGoogle Scholar
  128. 128.
    Smith A-S, Lorz BG, Goennenwein S, Sackmann E (2006) Force-controlled equilibria of specific vesicle-substrate adhesion. Biophys J 90:L52–L54PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Feder TJ, Weissmüller G, Žekš B, Sackmann E (1995) Spreading of giant vesicles on moderately adhesive substrates by fingering: a reflection interference contrast microscopy study. Phys Rev E 51(4):3427CrossRefGoogle Scholar
  130. 130.
    Albersdörfer A, Feder T, Sackmann E (1997) Adhesion-induced domain formation by interplay of long-range repulsion and short-range attraction force: a model membrane study. Biophys J 73:245–257PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Kloboucek A, Behrisch A, Faix J, Sackmann E (1999) Adhesion-induced receptor segregation and adhesion plaque formation: a model membrane study. Biophys J 77(4):2311–2328PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Nardi J, Bruinsma R, Sackmann E (1998) Adhesion-induced reorganization of charged fluid membranes. Phys Rev E 58(5):6340CrossRefGoogle Scholar
  133. 133.
    Solon J, Streicher P, Richter R, Brochard-Wyart F, Bassereau P (2006) Vesicles surfing on a lipid bilayer: self-induced haptotactic motion. Proc Natl Acad Sci U S A 103(33):12382–12387PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Sandre O, Moreaux L, Brochard-Wyart F (1999) Dynamics of transient pores in stretched vesicles. Proc Natl Acad Sci U S A 96(19):10591–10596PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Bernard A-L, Guedeau-Boudeville M-A, Sandre O, Palacin S, di Meglio J-M, Jullien L (2000) Permeation through lipid bilayers by adhesion of giant vesicles on decorated surfaces. Langmuir 16(17):6801–6808CrossRefGoogle Scholar
  136. 136.
    Puech P-H, Askovic V, De Gennes P-G, Brochard-Wyart F (2006) Dynamics of vesicle adhesion: spreading versus dewetting coupled to binder diffusion. Biophys Rev Lett 01(01):85–95CrossRefGoogle Scholar
  137. 137.
    Boulbitch A, Guttenberg Z, Sackmann E (2001) Kinetics of membrane adhesion mediated by ligand–receptor interaction studied with a biomimetic system. Biophys J 81:2743–2751PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Shenoy VB, Freund LB (2005) Growth and shape stability of a biological membrane adhesion complex in the diffusion-mediated regime. Proc Natl Acad Sci U S A 102:9CrossRefGoogle Scholar
  139. 139.
    Gao H, Shi W, Freund LB (2005) Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci U S A 102:27Google Scholar
  140. 140.
    Bihr T, Seifert U, Smith A-S (2015) Multiscale approaches to protein-mediated interactions between membranes—relating microscopic and macroscopic dynamics in radially growing adhesions. New J Phys 17(8):083016CrossRefGoogle Scholar
  141. 141.
    Brochard-Wyart F, De Gennes PG (2002) Adhesion induced by mobile binders: dynamics. Proc Natl Acad Sci U S A 99(12):7854–7859PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Guttenberg Z, Lorz B, Sackmann E, Boulbitch A (2001) First-order transition between adhesion states in a system mimicking cell-tissue interaction. Europhys Lett 54(6):826CrossRefGoogle Scholar
  143. 143.
    Cuvelier D, Nassoy P (2004) Hidden dynamics of vesicle adhesion induced by specific stickers. Phys Rev Lett 93(22):228101PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    De Gennes P-G, Puech P-H, Brochard-Wyart F (2003) Adhesion induced by mobile stickers: a list of scenarios. Langmuir 19:7112–7119CrossRefGoogle Scholar
  145. 145.
    Goennenwein S, Tanaka M, Hu B, Moroder L, Sackmann E (2003) Functional incorporation of integrins into solid supported membranes on ultrathin films of cellulose: impact on adhesion. Biophys J 85(1):646–655PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Streicher P, Nassoy P, Bärmann M, Dif A, Marchi-Artzner V, Brochard-Wyart F, Spatz J, Bassereau P (2009) Integrin reconstituted in guvs: a biomimetic system to study initial steps of cell spreading. Biochim Biophys Acta Biomembr 1788(10):2291–2300CrossRefGoogle Scholar
  147. 147.
    Puech P-H, Feracci H, Brochard-Wyart F (2004) Adhesion between giant vesicles and supported bilayers decorated with chelated e-cadherin fragments. Langmuir 20(22):9763–9768PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Saffman PG, Delbrück M (1975) Brownian motion in biological membranes. Proc Natl Acad Sci U S A 72:3111–3113PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Reister-Gottfried E, Sengupta K, Lorz B, Sackmann E, Seifert U, Smith A-S (2008) Dynamics of specific vesicle-substrate adhesion: from local events to global dynamics. Phys Rev Lett 101(20):208103:1–4Google Scholar
  150. 150.
    Naji A, Atzberger PJ, Brown FLH (2009) Hybrid elastic and discrete-particle approach to biomembrane dynamics with application to the mobility of curved integral membrane proteins. Phys Rev Lett 102:138102PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Reister-Gottfried E, Leitenberger SM, Seifert U (2010) Diffusing proteins on a fluctuating membrane: analytical theory and simulations. Phys Rev E 81:031903CrossRefGoogle Scholar
  152. 152.
    Quemeneur F, Sigurdsson JK, Renner M, Atzberger PJ, Bassereau P, Lacoste D (2014) Shape matters in protein mobility within membranes. Proc Natl Acad Sci U S A 111(14):5083–5087PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Bartossek T, Jones NG, Schäfer C, Cvitkovic M, Glogger M, Mott HR, Kuper J, Brennich M, Carrington M, Smith A-S, Fenz S, Kisker C, Engstler M (2017) Structural basis for the shielding function of the dynamic trypanosome variant surface glycoprotein coat. Nat Microbiol 2:1523–1532PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Deeg J, Axmann M, Matic J, Liapis A, Depoil D, Afrose J, Curado S, Dustin ML, Spatz JP (2013) T cell activation is determined by the number of presented antigens. Nano Lett 13(11):5619–5626. PMID: 24117051PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Deeg JA, Louban I, Aydin D, Selhuber-Unkel C, Kessler H, Spatz JP (2011) Impact of local versus global ligand density on cellular adhesion. Nano Lett 11(4):1469–1476. PMID: 21425841PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Smith A-S, Seifert U (2005) Force-induced de-adhesion of specifically bound vesicles: strong adhesion in competition with tether extraction. Langmuir 21(24):11357–11367. PMID: 16285811.PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Yu C-h, Rafiq NBM, Krishnasamy A, Hartman KL, Jones GE, Bershadsky AD, Sheetz MP (2013) Integrin-matrix clusters form podosome-like adhesions in the absence of traction forces. Cell Rep 5(5):1456–1468PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Fenz SF, Smith A-S, Merkel R, Sengupta K (2011) Inter-membrane adhesion mediated by mobile linkers: effect of receptor shortage. Soft Matter 7(3):952–962CrossRefGoogle Scholar
  159. 159.
    Shindell O, Mica N, Ritzer M, Gordon VD (2015) Specific adhesion of membranes simultaneously supports dual heterogeneities in lipids and proteins. Phys Chem Chem Phys 17:15598–15607PubMedCrossRefPubMedCentralGoogle Scholar
  160. 160.
    Bihr T, Sadafi F-Z, Seifert U, Taylor RK, Smith A-S (2017) Radial growth in 2d revisited: the effect of finite density, binding affinity, reaction rates, and diffusion. Adv Mater Int 4(1600310):1–7Google Scholar
  161. 161.
    Bell GI (1978) Models for the specific adhesion of cells to cells. Science 200:618–627PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Schmidt D, Bihr T, Seifert U, Smith A-S (2012) Coexistence of dilute and densely packed domains of ligand-receptor bonds in membrane adhesion. Europhys Lett 99:38003CrossRefGoogle Scholar
  163. 163.
    Erdmann T, Schwarz US (2006) Bistability of cell-matrix adhesions resulting from nonlinear receptor-ligand dynamics. Biophys J 91(6):L60–L62PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Evans E, Leung A, Heinrich V, Zhu C (2004) Mechanical switching and coupling between two dissociation pathways in a p-selectin adhesion bond. Proc Natl Acad Sci U S A 101(31):11281–11286PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Weikl TR (2001) Fluctuation-induced aggregation of rigid membrane inclusions. Europhys Lett 54:547–553CrossRefGoogle Scholar
  166. 166.
    Weikl TR, Andelman D, Komura S, Lipowsky R (2002) Adhesion of membranes with competing specific and generic interactions. Eur Phys J E 8:59–66PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Weikl TR, Lipowsky R (2004) Pattern formation during t-cell adhesion. Biophys J 87(6):3665–3678PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Weikl TR, Asfaw M, Krobath H, Rózycki B, Lipowsky R (2009) Adhesion of membranes via receptor–ligand complexes: domain formation, binding cooperativity, and active processes. Soft Matter 5:3213–3224CrossRefGoogle Scholar
  169. 169.
    Lin LC-L, Groves JT, Brown FLH (2006) Analysis of shape, fluctuations, and dynamics in intermembrane junctions. Biophys J 91:3600–3606PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Lin LC-L, Gov N, Brown FLH (2006) Nonequilibrium membrane fluctuations driven by active proteins. J Chem Phys 124(7):074903CrossRefGoogle Scholar
  171. 171.
    Reister E, Bihr T, Seifert U, Smith A-S (2011) Two intertwined facets of adherent membranes: membrane roughness and correlations between ligand–receptors bonds. New J Phys 13:025003:1–15Google Scholar
  172. 172.
    Fenz SF, Bihr T, Merkel R, Seifert U, Sengupta K, Smith A-S (2011) Switching from ultraweak to strong adhesion. Adv Mater 27:2622–2626CrossRefGoogle Scholar
  173. 173.
    Farago O (2008) Membrane fluctuations near a plane rigid surface. Phys Rev E 78:051919CrossRefGoogle Scholar
  174. 174.
    Farago O (2010) Fluctuation-induced attraction between adhesion sites of supported membranes. Phys Rev E 81(5):050902CrossRefGoogle Scholar
  175. 175.
    Speck T, Reister E, Seifert U (2010) Specific adhesion of membranes: mapping to an effective bond lattice gas. Phys Rev E 82:021923CrossRefGoogle Scholar
  176. 176.
    Dustin M, Bromley SK, Davis MM, Zhu C (2001) Identification of self through two-dimensional chemistry and synapses. Annu Rev Cell Dev Biol 17(3):133–157PubMedCrossRefPubMedCentralGoogle Scholar
  177. 177.
    Zhu D-M, Dustin ML, Cairo CW, Golan DE (2007) Analysis of two-dimensional dissociation constant of laterally mobile cell adhesion molecules. Biophys J 92(3):1022–1034PubMedCrossRefPubMedCentralGoogle Scholar
  178. 178.
    Hu J, Lipowsky R, Weikl TR (2013) Binding constants of membrane-anchored receptors and ligands depend strongly on the nanoscale roughness of membranes. Proc Natl Acad Sci U S A 110:15283–15288PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Perez TD, Tamada M, Sheetz MP, Nelson WJ (2008) Immediate-early signaling induced by E-cadherin engagement and adhesion. J Biol Chem 283(8):5014–5022PubMedCrossRefPubMedCentralGoogle Scholar
  180. 180.
    Bazellières E, Conte V, Elosegui-Artola A, Serra-Picamal X, Bintanel-Morcillo M, Roca-Cusachs P, Muñoz JJ, Sales-Pardo M, Guimerà R, Trepat X (2015) Control of cell–cell forces and collective cell dynamics by the intercellular adhesome. Nat Cell Biol 17(4):409–420PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Aix-Marseille UniversitéCNRS, CINaM UMR 7325Marseille cedex 9France
  2. 2.PULS Group, Institut für Theoretische Physik and the Excellence Cluster: Engineering of Advanced MaterialsUniversität Erlangen-NürnbergErlangenGermany
  3. 3.Institute Ruđer BoškovićDivision of Physical ChemistryZagrebCroatia

Personalised recommendations