Skip to main content
SpringerLink
Log in

Spatial and Mechanical Aspects of Signal Transduction in the Cell Membrane

  • Chapter
  • First Online:
Physics of Biological Membranes

Abstract

Intercellular cognate receptor-ligand pairs are major players in cellular signal transduction. The fact that both the receptor and the ligand are present on the membrane in these juxtacrine signaling interactions presents distinct experimental difficulties in their study. One experimental platform that has proven particularly useful is the hybrid live cell-supported lipid bilayer system, wherein a live cell is allowed to interact with a synthetic supported membrane displaying ligands of interest. A synthetic membrane enables control over identity, density, mobility, and spatial patterning of the displayed ligands. This chapter provides insights gained from the reconstitution of the immunological synapse formed by T-cells, junction formed by ephrinA1-EphA2 receptor tyrosine kinase in breast cancer cells, and adhesion formed by E-cadherin in epithelial cells on synthetic supported lipid bilayers.

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

Access this chapter

Log in via an institution
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. Bromley SK, Burack WR, Johnson KG, Somersalo K, Sims TN, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (2001) The immunological synapse. Annu Rev Immunol 19:375–396. https://doi.org/10.1146/annurev.immunol.19.1.375

    Article  CAS  PubMed  Google Scholar 

  2. 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):221–227. https://doi.org/10.1126/science.285.5425.221

    Article  CAS  PubMed  Google Scholar 

  3. Mossman KD, Campi G, Groves JT, Dustin ML (2005) Altered TCR signaling from geometrically repatterned immunological synapses. Science 310(5751):1191–1193. https://doi.org/10.1126/science.1119238

    Article  CAS  PubMed  Google Scholar 

  4. Klein R (2012) Eph/ephrin signalling during development. Development 139(22):4105–4109. https://doi.org/10.1242/dev.074997

    Article  CAS  PubMed  Google Scholar 

  5. Murai KK, Pasquale EB (2003) `Eph'ective signaling: forward, reverse and crosstalk. J Cell Sci 116(Pt 14):2823–2832. https://doi.org/10.1242/jcs.00625

    Article  CAS  PubMed  Google Scholar 

  6. Leckband DE, de Rooij J (2014) Cadherin adhesion and mechanotransduction. Annu Rev Cell Dev Biol 30:291–315. https://doi.org/10.1146/annurev-cellbio-100913-013212

    Article  CAS  PubMed  Google Scholar 

  7. Patel SD, Chen CP, Bahna F, Honig B, Shapiro L (2003) Cadherin-mediated cell-cell adhesion: sticking together as a family. Curr Opin Struct Biol 13(6):690–698

    Article  CAS  PubMed  Google Scholar 

  8. Wheelock MJ, Johnson KR (2003) Cadherin-mediated cellular signaling. Curr Opin Cell Biol 15(5):509–514. https://doi.org/10.1016/S0955-0674(03)00101-7

    Article  CAS  PubMed  Google Scholar 

  9. Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284(5415):770–776

    Article  CAS  PubMed  Google Scholar 

  10. Kopan R (2012) Notch signaling. Cold Spring Harb Perspect Biol 4(10). https://doi.org/10.1101/cshperspect.a011213

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sackmann E (1996) Supported membranes: scientific and practical applications. Science 271(5245):43–48. https://doi.org/10.1126/science.271.5245.43

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka M, Sackmann E (2005) Polymer-supported membranes as models of the cell surface. Nature 437(7059):656–663. https://doi.org/10.1038/nature04164

    Article  CAS  PubMed  Google Scholar 

  13. Groves JT, Boxer SG (1995) Electric field-induced concentration gradients in planar supported bilayers. Biophys J 69(5):1972–1975. https://doi.org/10.1016/S0006-3495(95)80067-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Groves JT, Boxer SG (2002) Micropattern formation in supported lipid membranes. Acc Chem Res 35(3):149–157. https://doi.org/10.1021/ar950039m

    Article  CAS  PubMed  Google Scholar 

  15. Groves JT, Ulman N, Boxer SG (1997) Micropatterning fluid lipid bilayers on solid supports. Science 275(5300):651–653. https://doi.org/10.1126/science.275.5300.651

    Article  CAS  PubMed  Google Scholar 

  16. Groves JT, Wulfing C, Boxer SG (1996) Electrical manipulation of glycan-phosphatidyl inositol-tethered proteins in planar supported bilayers. Biophys J 71(5):2716–2723. https://doi.org/10.1016/S0006-3495(96)79462-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Caculitan NG, Kai H, Liu E, Fay N, Yu Y, Lohmuller T, O'Donoghue GP, Groves JT (2014) Size-based chromatography of signaling clusters in a living cell membrane. Nano Lett 14(5):2293–2298. https://doi.org/10.1021/nl404514e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. DeMond AL, Mossman KD, Starr T, Dustin ML, Groves JT (2008) T cell receptor microcluster transport through molecular mazes reveals mechanism of translocation. Biophys J 94(8):3286–3292. https://doi.org/10.1529/biophysj.107.119099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yu CH, Wu HJ, Kaizuka Y, Vale RD, Groves JT (2010) Altered actin centripetal retrograde flow in physically restricted immunological synapses. PLoS One 5(7):e11878. https://doi.org/10.1371/journal.pone.0011878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yu Y, Fay NC, Smoligovets AA, Wu HJ, Groves JT (2012) Myosin IIA modulates T cell receptor transport and CasL phosphorylation during early immunological synapse formation. PLoS One 7(2):e30704. https://doi.org/10.1371/journal.pone.0030704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ketchum C, Miller H, Song W, Upadhyaya A (2014) Ligand mobility regulates B cell receptor clustering and signaling activation. Biophys J 106(1):26–36. https://doi.org/10.1016/j.bpj.2013.10.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu W, Won Sohn H, Tolar P, Meckel T, Pierce SK (2010) Antigen-induced oligomerization of the B cell receptor is an early target of fc gamma RIIB inhibition. J Immunol 184(4):1977–1989. https://doi.org/10.4049/jimmunol.0902334

    Article  CAS  PubMed  Google Scholar 

  23. Natkanski E, Lee WY, Mistry B, Casal A, Molloy JE, Tolar P (2013) B cells use mechanical energy to discriminate antigen affinities. Science 340(6140):1587–1590. https://doi.org/10.1126/science.1237572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Greene AC, Lord SJ, Tian A, Rhodes C, Kai H, Groves JT (2014) Spatial organization of EphA2 at the cell-cell interface modulates trans-endocytosis of ephrinA1. Biophys J 106(10):2196–2205. https://doi.org/10.1016/j.bpj.2014.03.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lohmuller T, Xu Q, Groves JT (2013) Nanoscale obstacle arrays frustrate transport of EphA2-Ephrin-A1 clusters in cancer cell lines. Nano Lett 13(7):3059–3064. https://doi.org/10.1021/nl400874v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Salaita K, Nair PM, Petit RS, Neve RM, Das D, Gray JW, Groves JT (2010) Restriction of receptor movement alters cellular response: physical force sensing by EphA2. Science 327(5971):1380–1385. https://doi.org/10.1126/science.1181729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Baksh MM, Dean C, Pautot S, DeMaria S, Isacoff E, Groves JT (2005) Neuronal activation by GPI-linked neuroligin-1 displayed in synthetic lipid bilayer membranes. Langmuir 21(23):10693–10698. https://doi.org/10.1021/la051243d

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pautot S, Lee H, Isacoff EY, Groves JT (2005) Neuronal synapse interaction reconstituted between live cells and supported lipid bilayers. Nat Chem Biol 1(5):283–289. https://doi.org/10.1038/nchembio737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yu CH, Law JB, Suryana M, Low HY, Sheetz MP (2011) Early integrin binding to Arg-Gly-asp peptide activates actin polymerization and contractile movement that stimulates outward translocation. Proc Natl Acad Sci USA 108(51):20585–20590. https://doi.org/10.1073/pnas.1109485108

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yu CH, Rafiq NB, Cao F, Zhou Y, Krishnasamy A, Biswas KH, Ravasio A, Chen Z, Wang YH, Kawauchi K, Jones GE, Sheetz MP (2015) Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force. Nat Commun 6:8672. https://doi.org/10.1038/ncomms9672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yu CH, Rafiq NB, 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):1456–1468. https://doi.org/10.1016/j.celrep.2013.10.040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Vafaei S, Tabaei SR, Biswas KH, Groves JT, Cho N-J (2017) Dynamic cellular interactions with extracellular matrix triggered by biomechanical tuning of low-rigidity, supported lipid membranes. Adv Healthc Mater 6(10):1700243–n/a. https://doi.org/10.1002/adhm.201770049

    Article  CAS  Google Scholar 

  33. Biswas KH, Hartman KL, Yu CH, Harrison OJ, Song H, Smith AW, Huang WY, Lin WC, Guo Z, Padmanabhan A, Troyanovsky SM, Dustin ML, Shapiro L, Honig B, Zaidel-Bar R, Groves JT (2015) E-cadherin junction formation involves an active kinetic nucleation process. Proc Natl Acad Sci USA 112(35):10932–10937. https://doi.org/10.1073/pnas.1513775112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Biswas KH, Hartman KL, Zaidel-Bar R, Groves JT (2016) Sustained alpha-catenin activation at E-cadherin junctions in the absence of mechanical force. Biophys J 111(5):1044–1052. https://doi.org/10.1016/j.bpj.2016.06.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Davis MM, Boniface JJ, Reich Z, Lyons D, Hampl J, Arden B, Chien Y (1998) Ligand recognition by alpha beta T cell receptors. Annu Rev Immunol 16:523–544. https://doi.org/10.1146/annurev.immunol.16.1.523

    Article  CAS  PubMed  Google Scholar 

  36. Wang W, Gulden PH, Pierce RA, Shabanowitz J, Man ST, Hunt DF, Engelhard VH (1997) A naturally processed peptide presented by HLA-A*0201 is expressed at low abundance and recognized by an alloreactive CD8+ cytotoxic T cell with apparent high affinity. J Immunol 158(12):5797–5804

    CAS  PubMed  Google Scholar 

  37. Brian AA, McConnell HM (1984) Allogeneic stimulation of cytotoxic T cells by supported planar membranes. Proc Natl Acad Sci USA 81(19):6159–6163. https://doi.org/10.1073/pnas.81.19.6159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Salafsky J, Groves JT, Boxer SG (1996) Architecture and function of membrane proteins in planar supported bilayers: a study with photosynthetic reaction centers. Biochemistry 35(47):14773–14781. https://doi.org/10.1021/bi961432i

    Article  CAS  PubMed  Google Scholar 

  39. Hartman NC, Nye JA, Groves JT (2009) Cluster size regulates protein sorting in the immunological synapse. Proc Natl Acad Sci USA 106(31):12729–12734. https://doi.org/10.1073/pnas.0902621106

    Article  PubMed  PubMed Central  Google Scholar 

  40. Manz BN, Jackson BL, Petit RS, Dustin ML, Groves J (2011) T-cell triggering thresholds are modulated by the number of antigen within individual T-cell receptor clusters. Proc Natl Acad Sci USA 108(22):9089–9094. https://doi.org/10.1073/pnas.1018771108

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yu CH, Groves JT (2010) Engineering supported membranes for cell biology. Med Biol Eng Comput 48(10):955–963. https://doi.org/10.1007/s11517-010-0634-x

    Article  PubMed  PubMed Central  Google Scholar 

  42. Groves JT (2006) Spatial mutation of the T cell immunological synapse. Curr Opin Chem Biol 10(6):544–550. https://doi.org/10.1016/j.cbpa.2006.10.021

    Article  CAS  PubMed  Google Scholar 

  43. Hsu CJ, Hsieh WT, Waldman A, Clarke F, Huseby ES, Burkhardt JK, Baumgart T (2012) Ligand mobility modulates immunological synapse formation and T cell activation. PLoS One 7(2):e32398. https://doi.org/10.1371/journal.pone.0032398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Choudhuri K, Llodra J, Roth EW, Tsai J, Gordo S, Wucherpfennig KW, Kam LC, Stokes DL, Dustin ML (2014) Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature 507(7490):118–123. https://doi.org/10.1038/nature12951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Caplan S, Zeliger S, Wang L, Baniyash M (1995) Cell-surface-expressed T-cell antigen-receptor zeta chain is associated with the cytoskeleton. Proc Natl Acad Sci USA 92(11):4768–4772. https://doi.org/10.1073/pnas.1512331113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wulfing C, Davis MM (1998) A receptor/cytoskeletal movement triggered by costimulation during T cell activation. Science 282(5397):2266–2269. https://doi.org/10.1126/science.282.5397.2266

    Article  CAS  PubMed  Google Scholar 

  47. Smoligovets AA, Smith AW, Wu HJ, Petit RS, Groves JT (2012) Characterization of dynamic actin associations with T-cell receptor microclusters in primary T cells. J Cell Sci 125(Pt 3):735–742. https://doi.org/10.1242/jcs.092825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Choudhuri K, Wiseman D, Brown MH, Gould K, van der Merwe PA (2005) T-cell receptor triggering is critically dependent on the dimensions of its peptide-MHC ligand. Nature 436(7050):578–582. https://doi.org/10.1038/nature03843

    Article  CAS  PubMed  Google Scholar 

  49. Cordoba SP, Choudhuri K, Zhang H, Bridge M, Basat AB, Dustin ML, van der Merwe PA (2013) The large ectodomains of CD45 and CD148 regulate their segregation from and inhibition of ligated T-cell receptor. Blood 121(21):4295–4302. https://doi.org/10.1182/blood-2012-07-442251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. James JR, Vale RD (2012) Biophysical mechanism of T-cell receptor triggering in a reconstituted system. Nature 487(7405):64–69. https://doi.org/10.1038/nature11220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lim HS, Cordoba SP, Dushek O, Goyette J, Taylor A, Rudd CE, van der Merwe PA (2015) Costimulation of IL-2 production through CD28 is dependent on the size of its ligand. J Immunol 195(11):5432–5439. https://doi.org/10.4049/jimmunol.1500707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Milstein O, Tseng SY, Starr T, Llodra J, Nans A, Liu M, Wild MK, van der Merwe PA, Stokes DL, Reisner Y, Dustin ML (2008) Nanoscale increases in CD2-CD48-mediated intermembrane spacing decrease adhesion and reorganize the immunological synapse. J Biol Chem 283(49):34414–34422. https://doi.org/10.1074/jbc.M804756200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. O'Donoghue GP, Pielak RM, Smoligovets AA, Lin JJ, Groves JT (2013) Direct single molecule measurement of TCR triggering by agonist pMHC in living primary T cells. eLife 2:e00778. https://doi.org/10.7554/eLife.00778

    Article  PubMed  PubMed Central  Google Scholar 

  54. Corse E, Gottschalk RA, Krogsgaard M, Allison JP (2010) Attenuated T cell responses to a high-potency ligand in vivo. PLoS Biol 8(9). https://doi.org/10.1371/journal.pbio.1000481

    Article  PubMed  PubMed Central  Google Scholar 

  55. Newell EW, Ely LK, Kruse AC, Reay PA, Rodriguez SN, Lin AE, Kuhns MS, Garcia KC, Davis MM (2011) Structural basis of specificity and cross-reactivity in T cell receptors specific for cytochrome c-I-E(k). J Immunol 186(10):5823–5832. https://doi.org/10.4049/jimmunol.1100197

    Article  CAS  PubMed  Google Scholar 

  56. Huppa JB, Axmann M, Mortelmaier MA, Lillemeier BF, Newell EW, Brameshuber M, Klein LO, Schutz GJ, Davis MM (2010) TCR-peptide-MHC interactions in situ show accelerated kinetics and increased affinity. Nature 463(7283):963–967. https://doi.org/10.1038/nature08746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mosch B, Reissenweber B, Neuber C, Pietzsch J (2010) Eph receptors and ephrin ligands: important players in angiogenesis and tumor angiogenesis. J Oncol 2010:135285. https://doi.org/10.1155/2010/135285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Miura K, Nam JM, Kojima C, Mochizuki N, Sabe H (2009) EphA2 engages Git1 to suppress Arf6 activity modulating epithelial cell-cell contacts. Mol Biol Cell 20(7):1949–1959. https://doi.org/10.1091/mbc.E08-06-0549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bashaw GJ, Klein R (2010) Signaling from axon guidance receptors. Cold Spring Harb Perspect Biol 2(5):a001941. https://doi.org/10.1101/cshperspect.a001941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Fang WB, Ireton RC, Zhuang G, Takahashi T, Reynolds A, Chen J (2008) Overexpression of EPHA2 receptor destabilizes adherens junctions via a RhoA-dependent mechanism. J Cell Sci 121(Pt 3):358–368. https://doi.org/10.1242/jcs.017145

    Article  CAS  PubMed  Google Scholar 

  61. Pasquale EB (2008) Eph-ephrin bidirectional signaling in physiology and disease. Cell 133(1):38–52. https://doi.org/10.1016/j.cell.2008.03.011

    Article  CAS  PubMed  Google Scholar 

  62. Salaita K, Groves JT (2010) Roles of the cytoskeleton in regulating EphA2 signals. Commun Integr Biol 3(5):454–457. https://doi.org/10.4161/cib.3.5.12418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Seiradake E, Harlos K, Sutton G, Aricescu AR, Jones EY (2010) An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. Nat Struct Mol Biol 17(4):398–402. https://doi.org/10.1038/nsmb.1782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Himanen JP, Yermekbayeva L, Janes PW, Walker JR, Xu K, Atapattu L, Rajashankar KR, Mensinga A, Lackmann M, Nikolov DB, Dhe-Paganon S (2010) Architecture of Eph receptor clusters. Proc Natl Acad Sci USA 107(24):10860–10865. https://doi.org/10.1073/pnas.1004148107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Seiradake E, Schaupp A, del Toro Ruiz D, Kaufmann R, Mitakidis N, Harlos K, Aricescu AR, Klein R, Jones EY (2013) Structurally encoded intraclass differences in EphA clusters drive distinct cell responses. Nat Struct Mol Biol 20(8):958–964. https://doi.org/10.1038/nsmb.2617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T, Goldfarb M, Yancopoulos GD (1994) Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science 266(5186):816–819. https://doi.org/10.1126/science.7973638

    Article  CAS  PubMed  Google Scholar 

  67. Atapattu L, Saha N, Llerena C, Vail ME, Scott AM, Nikolov DB, Lackmann M, Janes PW (2012) Antibodies binding the ADAM10 substrate recognition domain inhibit Eph function. J Cell Sci 125(Pt 24):6084–6093. https://doi.org/10.1242/jcs.112631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB (2005) Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 123(2):291–304. https://doi.org/10.1016/j.cell.2005.08.014

    Article  CAS  PubMed  Google Scholar 

  69. Lohmuller T, Triffo S, O'Donoghue GP, Xu Q, Coyle MP, Groves JT (2011) Supported membranes embedded with fixed arrays of gold nanoparticles. Nano Lett 11(11):4912–4918. https://doi.org/10.1021/nl202847t

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Schmid EM, Bakalar MH, Choudhuri K, Weichsel J, Ann H, Geissler PL, Dustin ML, Fletcher DA (2016) Size-dependent protein segregation at membrane interfaces. Nat Phys 12(7):704–711. https://doi.org/10.1038/nphys3678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Biswas KH, Groves JT (2016) A microbead supported membrane-based fluorescence imaging assay reveals intermembrane receptor-ligand complex dimension with nanometer precision. Langmuir 32(26):6775–6780. https://doi.org/10.1021/acs.langmuir.6b01377

    Article  CAS  PubMed  Google Scholar 

  72. Dutta D, Williamson CD, Cole NB, Donaldson JG (2012) Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis. PLoS One 7(9):e45799. https://doi.org/10.1371/journal.pone.0045799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. von Kleist L, Stahlschmidt W, Bulut H, Gromova K, Puchkov D, Robertson MJ, MacGregor KA, Tomilin N, Pechstein A, Chau N, Chircop M, Sakoff J, von Kries JP, Saenger W, Krausslich HG, Shupliakov O, Robinson PJ, McCluskey A, Haucke V (2011) Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell 146(3):471–484. https://doi.org/10.1016/j.cell.2011.06.025

    Article  CAS  Google Scholar 

  74. Fridman JS, Caulder E, Hansbury M, Liu X, Yang G, Wang Q, Lo Y, Zhou BB, Pan M, Thomas SM, Grandis JR, Zhuo J, Yao W, Newton RC, Friedman SM, Scherle PA, Vaddi K (2007) Selective inhibition of ADAM metalloproteases as a novel approach for modulating ErbB pathways in cancer. Clin Cancer Res 13(6):1892–1902. https://doi.org/10.1158/1078-0432.CCR-06-2116

    Article  CAS  PubMed  Google Scholar 

  75. Zhou BB, Peyton M, He B, Liu C, Girard L, Caudler E, Lo Y, Baribaud F, Mikami I, Reguart N, Yang G, Li Y, Yao W, Vaddi K, Gazdar AF, Friedman SM, Jablons DM, Newton RC, Fridman JS, Minna JD, Scherle PA (2006) Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer. Cancer Cell 10(1):39–50. https://doi.org/10.1016/j.ccr.2006.05.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Brasch J, Harrison OJ, Honig B, Shapiro L (2012) Thinking outside the cell: how cadherins drive adhesion. Trends Cell Biol 22(6):299–310. https://doi.org/10.1016/j.tcb.2012.03.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hiroki O (2012) Evolution of the cadherin-catenin complex. Subcell Biochem 60:9–35. https://doi.org/10.1007/978-94-007-4186-7_2

    Article  CAS  PubMed  Google Scholar 

  78. Biswas KH, Zaidel-Bar R (2017) Early events in the assembly of E-cadherin adhesions. Exp Cell Res 358(1):14–19. https://doi.org/10.1016/j.yexcr.2017.02.037

    Article  CAS  PubMed  Google Scholar 

  79. 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):244–256. https://doi.org/10.1016/j.str.2010.11.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Larue L, Ohsugi M, Hirchenhain J, Kemler R (1994) E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci USA 91(17):8263–8267. https://doi.org/10.1073/pnas.91.17.8263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Riethmacher D, Brinkmann V, Birchmeier C (1995) A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. Proc Natl Acad Sci USA 92(3):855–859. https://doi.org/10.1073/pnas.92.3.855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392(6674):402–405. https://doi.org/10.1038/32918

    Article  CAS  PubMed  Google Scholar 

  83. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA (2008) Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res 68(10):3645–3654. https://doi.org/10.1158/0008-5472.CAN-07-2938

    Article  CAS  PubMed  Google Scholar 

  84. van Roy F (2014) Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer 14(2):121–134. https://doi.org/10.1038/nrc3647

    Article  CAS  PubMed  Google Scholar 

  85. Vasioukhin V (2012) Adherens junctions and cancer. Subcell Biochem 60:379–414. https://doi.org/10.1007/978-94-007-4186-7_16

    Article  CAS  PubMed  Google Scholar 

  86. Ciatto C, Bahna F, Zampieri N, VanSteenhouse HC, Katsamba PS, Ahlsen G, Harrison OJ, Brasch J, Jin X, Posy S, Vendome J, Ranscht B, Jessell TM, Honig B, Shapiro L (2010) T-cadherin structures reveal a novel adhesive binding mechanism. Nat Struct Mol Biol 17(3):339–347. https://doi.org/10.1038/nsmb.1781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Harrison OJ, Bahna F, Katsamba PS, Jin X, Brasch J, Vendome J, Ahlsen G, Carroll KJ, Price SR, Honig B, Shapiro L (2010) Two-step adhesive binding by classical cadherins. Nat Struct Mol Biol 17(3):348–357. https://doi.org/10.1038/nsmb.1784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Haussinger D, Ahrens T, Aberle T, Engel J, Stetefeld J, Grzesiek S (2004) Proteolytic E-cadherin activation followed by solution NMR and X-ray crystallography. EMBO J 23(8):1699–1708. https://doi.org/10.1038/sj.emboj.7600192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. 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 USA 106(28):11594–11599. https://doi.org/10.1073/pnas.0905349106

    Article  PubMed  PubMed Central  Google Scholar 

  90. Koch AW, Pokutta S, Lustig A, Engel J (1997) Calcium binding and homoassociation of E-cadherin domains. Biochemistry 36(25):7697–7705. https://doi.org/10.1021/bi9705624

    Article  CAS  PubMed  Google Scholar 

  91. Li Y, Altorelli NL, Bahna F, Honig B, Shapiro L, Palmer AG 3rd (2013) Mechanism of E-cadherin dimerization probed by NMR relaxation dispersion. Proc Natl Acad Sci USA 110(41):16462–16467. https://doi.org/10.1073/pnas.1314303110

    Article  PubMed  PubMed Central  Google Scholar 

  92. Bunse S, Garg S, Junek S, Vogel D, Ansari N, Stelzer EH, Schuman E (2013) Role of N-cadherin cis and trans interfaces in the dynamics of adherens junctions in living cells. PLoS One 8(12):e81517. https://doi.org/10.1371/journal.pone.0081517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Wu Y, Jin X, Harrison O, Shapiro L, Honig BH, Ben-Shaul A (2010) Cooperativity between trans and cis interactions in cadherin-mediated junction formation. Proc Natl Acad Sci USA 107(41):17592–17597. https://doi.org/10.1073/pnas.1011247107

    Article  PubMed  PubMed Central  Google Scholar 

  94. 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):510–513. https://doi.org/10.1038/nature10183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Nagar B, Overduin M, Ikura M, Rini JM (1996) Structural basis of calcium-induced E-cadherin rigidification and dimerization. Nature 380(6572):360–364. https://doi.org/10.1038/380360a0

    Article  CAS  PubMed  Google Scholar 

  96. Pertz O, Bozic D, Koch AW, Fauser C, Brancaccio A, Engel J (1999) A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation. EMBO J 18(7):1738–1747. https://doi.org/10.1093/emboj/18.7.1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Sivasankar S, Zhang Y, Nelson WJ, Chu S (2009) Characterizing the initial encounter complex in cadherin adhesion. Structure 17(8):1075–1081. https://doi.org/10.1016/j.str.2009.06.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Hong S, Troyanovsky RB, Troyanovsky SM (2011) Cadherin exits the junction by switching its adhesive bond. J Cell Biol 192(6):1073–1083. https://doi.org/10.1083/jcb.201006113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Rakshit S, Zhang Y, Manibog K, Shafraz O, Sivasankar S (2012) Ideal, catch, and slip bonds in cadherin adhesion. Proc Natl Acad Sci USA 109(46):18815–18820. https://doi.org/10.1073/pnas.1208349109

    Article  PubMed  PubMed Central  Google Scholar 

  100. Bertocchi C, Wang Y, Ravasio A, Hara Y, Wu Y, Sailov T, Baird MA, Davidson MW, Zaidel-Bar R, Toyama Y, Ladoux B, Mege RM, Kanchanawong P (2017) Nanoscale architecture of cadherin-based cell adhesions. Nat Cell Biol 19(1):28–37. https://doi.org/10.1038/ncb3456

    Article  CAS  PubMed  Google Scholar 

  101. Guo Z, Neilson LJ, Zhong H, Murray PS, Zanivan S, Zaidel-Bar R (2014) E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Sci Signal 7(354):rs7. https://doi.org/10.1126/scisignal.2005473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. McEwen AE, Escobar DE, Gottardi CJ (2012) Signaling from the adherens junction. Subcell Biochem 60:171–196. https://doi.org/10.1007/978-94-007-4186-7_8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Van Itallie CM, Tietgens AJ, Aponte A, Fredriksson K, Fanning AS, Gucek M, Anderson JM (2014) Biotin ligase tagging identifies proteins proximal to E-cadherin, including lipoma preferred partner, a regulator of epithelial cell-cell and cell-substrate adhesion. J Cell Sci 127(Pt 4):885–895. https://doi.org/10.1242/jcs.140475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Zaidel-Bar R (2013) Cadherin adhesome at a glance. J Cell Sci 126(Pt 2):373–378. https://doi.org/10.1242/jcs.111559

    Article  CAS  PubMed  Google Scholar 

  105. Yonemura S, Wada Y, Watanabe T, Nagafuchi A, Shibata M (2010) Alpha-catenin as a tension transducer that induces adherens junction development. Nat Cell Biol 12(6):533–542. https://doi.org/10.1038/ncb2055

    Article  CAS  PubMed  Google Scholar 

  106. Buckley CD, Tan J, Anderson KL, Hanein D, Volkmann N, Weis WI, Nelson WJ, Dunn AR (2014) Cell adhesion. The minimal cadherin-catenin complex binds to actin filaments under force. Science 346(6209):1254211. https://doi.org/10.1126/science.1254211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Yao M, Qiu W, Liu R, Efremov AK, Cong P, Seddiki R, Payre M, Lim CT, Ladoux B, Mege RM, Yan J (2014) Force-dependent conformational switch of alpha-catenin controls vinculin binding. Nat Commun 5:4525. https://doi.org/10.1038/ncomms5525

    Article  CAS  PubMed  Google Scholar 

  108. le Duc Q, Shi Q, Blonk I, Sonnenberg A, Wang N, Leckband D, de Rooij J (2010) Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J Cell Biol 189(7):1107–1115. https://doi.org/10.1083/jcb.201001149

    Article  PubMed  PubMed Central  Google Scholar 

  109. Twiss F, Le Duc Q, Van Der Horst S, Tabdili H, Van Der Krogt G, Wang N, Rehmann H, Huveneers S, Leckband DE, De Rooij J (2012) Vinculin-dependent cadherin mechanosensing regulates efficient epithelial barrier formation. Biol Open 1(11):1128–1140. https://doi.org/10.1242/bio.20122428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Perez TD, Nelson WJ, Boxer SG, Kam L (2005) E-cadherin tethered to micropatterned supported lipid bilayers as a model for cell adhesion. Langmuir 21(25):11963–11968. https://doi.org/10.1021/la052264a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Andreasson-Ochsner M, Romano G, Hakanson M, Smith ML, Leckband DE, Textor M, Reimhult E (2011) Single cell 3-D platform to study ligand mobility in cell-cell contact. Lab Chip 11(17):2876–2883. https://doi.org/10.1039/c1lc20067d

    Article  CAS  PubMed  Google Scholar 

  112. McNeill H, Ozawa M, Kemler R, Nelson WJ (1990) Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity. Cell 62(2):309–316. https://doi.org/10.1016/0092-8674(90)90368-O

    Article  CAS  PubMed  Google Scholar 

  113. Charnley M, Kroschewski R, Textor M (2012) The study of polarisation in single cells using model cell membranes. Integr Biol 4(9):1059–1071. https://doi.org/10.1039/c2ib20111a

    Article  CAS  Google Scholar 

  114. Nye JA, Groves JT (2008) Kinetic control of histidine-tagged protein surface density on supported lipid bilayers. Langmuir 24(8):4145–4149. https://doi.org/10.1021/la703788h

    Article  CAS  PubMed  Google Scholar 

  115. Duguay D, Foty RA, Steinberg MS (2003) Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev Biol 253(2):309–323. https://doi.org/10.1016/S0012-1606(02)00016-7

    Article  CAS  PubMed  Google Scholar 

  116. Humpolickova J, Gielen E, Benda A, Fagulova V, Vercammen J, Vandeven M, Hof M, Ameloot M, Engelborghs Y (2006) Probing diffusion laws within cellular membranes by Z-scan fluorescence correlation spectroscopy. Biophys J 91(3):L23–L25. https://doi.org/10.1529/biophysj.106.089474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Chen Y, Muller JD, So PT, Gratton E (1999) The photon counting histogram in fluorescence fluctuation spectroscopy. Biophys J 77(1):553–567. https://doi.org/10.1016/S0006-3495(99)76912-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Lin WC, Iversen L, Tu HL, Rhodes C, Christensen SM, Iwig JS, Hansen SD, Huang WY, Groves JT (2014) H-Ras forms dimers on membrane surfaces via a protein-protein interface. Proc Natl Acad Sci USA 111(8):2996–3001. https://doi.org/10.1073/pnas.1321155111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Hong S, Troyanovsky RB, Troyanovsky SM (2013) Binding to F-actin guides cadherin cluster assembly, stability, and movement. J Cell Biol 201(1):131–143. https://doi.org/10.1083/jcb.201211054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Ozono K, Komiya S, Shimamura K, Ito T, Nagafuchi A (2011) Defining the roles of alpha-catenin in cell adhesion and cytoskeleton organization: isolation of F9 cells completely lacking cadherin-catenin complex. Cell Struct Funct 36(1):131–143. https://doi.org/10.1247/csf.11009

    Article  CAS  PubMed  Google Scholar 

  121. Iino R, Koyama I, Kusumi A (2001) Single molecule imaging of green fluorescent proteins in living cells: E-cadherin forms oligomers on the free cell surface. Biophys J 80(6):2667–2677. https://doi.org/10.1016/S0006-3495(01)76236-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Kusumi A, Nakada C, Ritchie K, Murase K, Suzuki K, Murakoshi H, Kasai RS, Kondo J, Fujiwara T (2005) Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules. Annu Rev Biophys Biomol Struct 34:351–378. https://doi.org/10.1146/annurev.biophys.34.040204.144637

    Article  CAS  PubMed  Google Scholar 

  123. 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(5):2021–2040. https://doi.org/10.1016/S0006-3495(93)81253-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sako Y, Nagafuchi A, Tsukita S, Takeichi M, Kusumi A (1998) Cytoplasmic regulation of the movement of E-cadherin on the free cell surface as studied by optical tweezers and single particle tracking: corralling and tethering by the membrane skeleton. J Cell Biol 140(5):1227–1240. https://doi.org/10.1083/jcb.140.5.1227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Sanchez MF, Levi V, Weidemann T, Carrer DC (2015) Agonist mobility on supported lipid bilayers affects Fas mediated death response. FEBS Lett 589(23):3527–3533. https://doi.org/10.1016/j.febslet.2015.10.009

    Article  CAS  PubMed  Google Scholar 

  126. Delanoe-Ayari H, Lenz P, Brevier J, Weidenhaupt M, Vallade M, Gulino D, Joanny JF, Riveline D (2004) Periodic adhesive fingers between contacting cells. Phys Rev Lett 93(10):108102. https://doi.org/10.1103/PhysRevLett.93.108102

    Article  CAS  PubMed  Google Scholar 

  127. Vasioukhin V, Bauer C, Yin M, Fuchs E (2000) Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 100(2):209–219. https://doi.org/10.1016/S0092-8674(00)81559-7

    Article  CAS  PubMed  Google Scholar 

  128. Jacquemet G, Hamidi H, Ivaska J (2015) Filopodia in cell adhesion, 3D migration and cancer cell invasion. Curr Opin Cell Biol 36:23–31. https://doi.org/10.1016/j.ceb.2015.06.007

    Article  CAS  PubMed  Google Scholar 

  129. Surviladze Z, Waller A, Strouse JJ, Bologa C, Ursu O, Salas V, Parkinson JF, Phillips GK, Romero E, Wandinger-Ness A, Sklar LA, Schroeder C, Simpson D, Noth J, Wang J, Golden J, Aube J (2010) A potent and selective inhibitor of Cdc42 GTPase. Probe Reports from the NIH Molecular Libraries Program, Bethesda, MD

    Google Scholar 

  130. Escobar DJ, Desai R, Ishiyama N, Folmsbee SS, Novak MN, Flozak AS, Daugherty RL, Mo R, Nanavati D, Sarpal R, Leckband D, Ikura M, Tepass U, Gottardi CJ (2015) Alpha-catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism. J Cell Sci 128(6):1150–1165. https://doi.org/10.1242/jcs.163824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore

    Kabir H. Biswas & Jay T. Groves

  2. Mechanobiology Institute, National University of Singapore, Singapore, Singapore

    Kabir H. Biswas

  3. Department of Chemistry, University of California, Berkeley, CA, USA

    Jay T. Groves

Authors
  1. Kabir H. Biswas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jay T. Groves
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kabir H. Biswas .

Editor information

Editors and Affiliations

  1. PhysicoChimie Curie (UMR CNRS 168), Institut Curie, Paris, France

    Patricia Bassereau

  2. PhysicoChimie Curie (UMR CNRS 168), Institut Curie, Paris, France

    Pierre Sens

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

Biswas, K.H., Groves, J.T. (2018). Spatial and Mechanical Aspects of Signal Transduction in the Cell Membrane. In: Bassereau, P., Sens, P. (eds) Physics of Biological Membranes. Springer, Cham. https://doi.org/10.1007/978-3-030-00630-3_19

Download citation

Publish with us

Policies and ethics

Search

Navigation