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Mechanobiology of collective cell behaviours

Nature Reviews Molecular Cell Biology volume 18, pages 743–757 (2017)Cite this article

Subjects

Key Points

  • In many biological situations in vivo, including tissue shaping during morphogenesis, tissue repair and cancer invasion, cells do not move as single bodies but as a collective.

  • Two main mechanisms support collective dynamics: polarized collective cell migration and coordinated contractile processes of cell groups that involve multicellular actomyosin-based structures.

  • In vitro wound-healing assays exploiting microfabricated devices have been models of choice to study collective cell behaviours. Such in vitro approaches are the most important methods to achieve multiscale analysis from the molecular to the multicellular level.

  • In contrast to a single cell, collective cell migration relies not only on the interactions with the extracellular matrix but also with neighbouring cells.

  • Coordinated movements strongly depend on intercellular interactions via mechanosensitive cadherin-based adhesions.

  • Cellular coordination is a mechanoregulated multiscale process integrating events at the molecular, cellular and multicellular scales, and it occurs at a wide range of timescales, from milliseconds to minutes to days.

Abstract

The way in which cells coordinate their behaviours during various biological processes, including morphogenesis, cancer progression and tissue remodelling, largely depends on the mechanical properties of the external environment. In contrast to single cells, collective cell behaviours rely on the cellular interactions not only with the surrounding extracellular matrix but also with neighbouring cells. Collective dynamics is not simply the result of many individually moving blocks. Instead, cells coordinate their movements by actively interacting with each other. These mechanisms are governed by mechanosensitive adhesion complexes at the cell–substrate interface and cell–cell junctions, which respond to but also further transmit physical signals. The mechanosensitivity and mechanotransduction at adhesion complexes are important for regulating tissue cohesiveness and thus are important for collective cell behaviours. Recent studies have shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces. On the basis of these findings, we can now start building our understanding of the mechanobiology of collective cell movements that span over multiple length scales from the molecular to the tissue level.

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Figure 1: Cell movements from single to collective dynamics.
Figure 2: Methods of force measurement.
Figure 3: Molecular coupling at intercellular contacts.
Figure 4: Physical constraints influencing collective cell behaviours.

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References

  1. Friedl, P. & Gilmour, D. Collective cell migration in morphogenesis, regeneration and cancer. Nat. Rev. Mol. Cell Biol. 10, 445–457 (2009).

    Article  CAS  PubMed  Google Scholar 

  2. Bianco, A. et al. Two distinct modes of guidance signalling during collective migration of border cells. Nature 448, 362–365 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Lecaudey, V., Cakan-Akdogan, G., Norton, W. H. & Gilmour, D. Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium. Development 135, 2695–2705 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Nabeshima, K., Inoue, T., Shimao, Y., Kataoka, H. & Koono, M. Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol. Histopathol. 14, 1183–1197 (1999).

    CAS  PubMed  Google Scholar 

  5. Einenkel, J., Braumann, U. D., Horn, L. C., Kuska, J. P. & Hockel, M. 3D analysis of the invasion front in squamous cell carcinoma of the uterine cervix: histopathologic evidence for collective invasion per continuitatem. Anal. Quantitative Cytol. Histol. 29, 279–290 (2007).

    Google Scholar 

  6. Giampieri, S. et al. Localized and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility. Nat. Cell Biol. 11, 1287–1296 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Behrndt, M. et al. Forces driving epithelial spreading in zebrafish gastrulation. Science 338, 257–260 (2012).

    Article  CAS  PubMed  Google Scholar 

  8. Abreu-Blanco, M. T., Verboon, J. M., Liu, R., Watts, J. J. & Parkhurst, S. M. Drosophila embryos close epithelial wounds using a combination of cellular protrusions and an actomyosin purse string. J. Cell Sci. 125, 5984–5997 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Campas, O. et al. Quantifying cell-generated mechanical forces within living embryonic tissues. Nat. Methods 11, 183–189 (2014). In this paper, the authors develop a method to measure the mechanical forces that cells exert while building tissues. They insert calibrated oil droplets in living embryos in contact with other cells. When cells push and pull on an oil droplet, they deform it, and this deformation provides a direct readout of the pressure they exert.

    Article  CAS  PubMed  Google Scholar 

  10. Bambardekar, K., Clement, R., Blanc, O., Chardes, C. & Lenne, P. F. Direct laser manipulation reveals the mechanics of cell contacts in vivo. Proc. Natl Acad. Sci. USA 112, 1416–1421 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hakim, V. & Silberzan, P. Collective cell migration: a physics perspective. Reports on progress in physics. Phys. Soc. 80, 076601 (2017).

    Google Scholar 

  12. Marchetti, M. C. et al. Hydrodynamics of soft active matter. Rev. Modern Phys. 85, 1143 (2013).

    Article  CAS  Google Scholar 

  13. Parsons, J. T., Horwitz, A. R. & Schwartz, M. A. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat. Rev. Mol. Cell Biol. 11, 633–643 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kanchanawong, P. et al. Nanoscale architecture of integrin-based cell adhesions. Nature 468, 580–584 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sarangi, B. R. et al. Coordination between intra- and extracellular forces regulates focal adhesion dynamics. Nano Lett. 17, 399–406 (2017).

    Article  CAS  PubMed  Google Scholar 

  16. Lo, C. M., Wang, H. B., Dembo, M. & Wang, Y. L. Cell movement is guided by the rigidity of the substrate. Biophys. J. 79, 144–152 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sniadecki, N. J. et al. Magnetic microposts as an approach to apply forces to living cells. Proc. Natl Acad. Sci. USA 104, 14553–14558 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Saxena, M. et al. EGFR and HER2 activate rigidity sensing only on rigid matrices. Nat. Mater. 16, 775–781 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ladoux, B., Mège, R. M. & Trepat, X. Front-rear polarization by mechanical cues: from single cells to tissues. Trends Cell Biol. 26, 420–433 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Cetera, M. et al. Epithelial rotation promotes the global alignment of contractile actin bundles during Drosophila egg chamber elongation. Nature Commun. 5, 5511 (2014). During the elongation of the D. melanogaster egg chamber into an ellipsoidal shape, the follicular epithelial cells undergo a collective migration that causes the egg chamber to rotate within its surrounding basement membrane. This study demonstrates that collective rotation plays a critical role in building up the actin-based component of a corset that forms during the elongation, in which actin bundles in the epithelium and fibrils in the basement membrane are all aligned perpendicular to the elongation axis.

    Article  CAS  Google Scholar 

  21. Bertet, C., Sulak, L. & Lecuit, T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667–671 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Dona, E. et al. Directional tissue migration through a self-generated chemokine gradient. Nature 503, 285–289 (2013).

    Article  CAS  PubMed  Google Scholar 

  23. Szabo, A. et al. In vivo confinement promotes collective migration of neural crest cells. J. Cell Biol. 213, 543–555 (2016). Combining computational and experimental approaches, the authors show that the in vivo collective migration of neural crest cells depends on confinement and geometrical constraints. They demonstrate that such confinement promotes directional migration of cell groups in vivo.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Haeger, A., Krause, M., Wolf, K. & Friedl, P. Cell jamming: collective invasion of mesenchymal tumor cells imposed by tissue confinement. Biochim. Biophys. Acta 1840, 2386–2395 (2014).

    Article  CAS  PubMed  Google Scholar 

  25. Abercrombie, M. & Ambrose, E. J. The surface properties of cancer cells: a review. Cancer Res. 22, 525–548 (1962).

    CAS  PubMed  Google Scholar 

  26. Poujade, M. et al. Collective migration of an epithelial monolayer in response to a model wound. Proc. Natl Acad. Sci. USA 104, 15988–15993 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Deforet, M. et al. Automated velocity mapping of migrating cell populations (AVeMap). Nat. Methods 9, 1081–1083 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. Mayor, R. & Etienne-Manneville, S. The front and rear of collective cell migration. Nat. Rev. Mol. Cell Biol. 17, 97–109 (2016).

    Article  CAS  PubMed  Google Scholar 

  29. Reffay, M. et al. Orientation and polarity in collectively migrating cell structures: statics and dynamics. Biophys. J. 100, 2566–2575 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Purcell, E. M. Life at low Reynolds number. Am. J. Phys. 45, 3–11 (1977).

    Article  Google Scholar 

  31. Vedula, S. R. K. et al. Emerging modes of collective cell migration induced by geometrical constraints. Proc. Natl Acad. Sci. USA 109, 12974–12979 (2012). In this study, the authors show that collective cell migration can be regulated by confinement. Cells migrate more quickly on narrow lines of the size of a single cell than on larger stripes of several cell diameters, and the mode of migration varies depending on the width of the micropatterned lines, consistent with different patterns of force transmission through cell–cell junctions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Foty, R. A. & Steinberg, M. S. The differential adhesion hypothesis: a direct evaluation. Dev. Biol. 278, 255–263 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Ranft, J. et al. Fluidization of tissues by cell division and apoptosis. Proc. Natl Acad. Sci. USA 107, 20863–20868 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lecuit, T. & Yap, A. S. E-Cadherin junctions as active mechanical integrators in tissue dynamics. Nat. Cell Biol. 17, 533–539 (2015).

    Article  CAS  PubMed  Google Scholar 

  35. Rossen, N. S., Tarp, J. M., Mathiesen, J., Jensen, M. H. & Oddershede, L. B. Long-range ordered vorticity patterns in living tissue induced by cell division. Nature Commun. 5, 5720 (2014). In this study, the authors analyse the dynamic movements of endothelial cells induced by cell division. Cell divisions induce long-range reorganization of cells together with the formation of vortex patterns that extend far away from the division site.

    Article  CAS  Google Scholar 

  36. Saw, T. B. et al. Topological defects in epithelia govern cell death and extrusion. Nature 544, 212–216 (2017). This paper shows that epithelial cells are elongated and closely packed, which means that they can spontaneously align in a similar way to the molecules in nematic liquid crystals. Accordingly, compressive stresses induced by oriented ordering and defects in the epithelium provide a physical trigger for cell extrusion and death.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Petitjean, L. et al. Velocity fields in a collectively migrating epithelium. Biophys. J. 98, 1790–1800 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Vedula, S. R. K. et al. Epithelial bridges maintain tissue integrity during collective cell migration. Nat. Mater. 13, 87–96 (2014).

    Article  CAS  PubMed  Google Scholar 

  39. Das, T. et al. A molecular mechanotransduction pathway regulates collective migration of epithelial cells. Nat. Cell Biol. 17, 276–287 (2015). In this study, the authors show that the protein Merlin is involved in coordinating motility forces from the edge into the bulk of the monolayer.

    Article  CAS  PubMed  Google Scholar 

  40. Bazellieres, E. et al. Control of cell-cell forces and collective cell dynamics by the intercellular adhesome. Nat. Cell Biol. 17, 409–420 (2015). The paper analyses the role of molecules at desmosomes, tight junctions and adherens junctions involved in cell–cell interactions in the establishment of forces and stresses during collective cell migration. It also shows that E-cadherins and P-cadherins respond to the level of force or to the rate at which the intercellular stress builds up, respectively, which allows for a particularly efficient control of mechanosensation at cadherin-based junctions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Basan, M., Elgeti, J., Hannezo, E., Rappel, W. J. & Levine, H. Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing. Proc. Natl Acad. Sci. USA 110, 2452–2459 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Farooqui, R. & Fenteany, G. Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement. J. Cell Sci. 118, 51–63 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Takeichi, M. Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling. Nat. Rev. Mol. Cell Biol. 15, 397–410 (2014).

    Article  CAS  PubMed  Google Scholar 

  44. Brugues, A. et al. Forces driving epithelial wound healing. Nat. Phys. 10, 684–691 (2014).

    Article  CAS  Google Scholar 

  45. Vedula, S. R. K. et al. Mechanics of epithelial closure over non-adherent environments. Nat. Commun. 6, 6111 (2015).

    Article  CAS  PubMed  Google Scholar 

  46. Clark, A. G. et al. Integration of single and multicellular wound responses. Curr. Biol. 19, 1389–1395 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wood, W. et al. Wound healing recapitulates morphogenesis in Drosophila embryos. Nat. Cell Biol. 4, 907–912 (2002).

    Article  CAS  PubMed  Google Scholar 

  48. Tamada, M., Perez, T. D., Nelson, W. J. & Sheetz, M. P. Two distinct modes of myosin assembly and dynamics during epithelial wound closure. J. Cell Biol. 176, 27–33 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Anon, E. et al. Cell crawling mediates collective cell migration to close undamaged epithelial gaps. Proc. Natl Acad. Sci. USA 109, 10891–10896 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Cochet-Escartin, O., Ranft, J., Silberzan, P. & Marcq, P. Border forces and friction control epithelial closure dynamics. Biophys. J. 106, 65–73 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Vitorino, P. & Meyer, T. Modular control of endothelial sheet migration. Genes Dev. 22, 3268–3281 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ng, M. R., Besser, A., Danuser, G. & Brugge, J. S. Substrate stiffness regulates cadherin-dependent collective migration through myosin-II contractility. J. Cell Biol. 199, 545–563 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gumbiner, B. Generation and maintenance of epithelial cell polarity. Curr. Opin. Cell Biol. 2, 881–887 (1990).

    Article  CAS  PubMed  Google Scholar 

  54. Sunyer, R. et al. Collective cell durotaxis emerges from long-range intercellular force transmission. Science 353, 1157–1161 (2016). In this study, the authors show that collective cell migration can be regulated by substrate stiffness, with cells moving towards stiff substrates — cells on a stiffer substrate have more resistance, enabling them to generate higher traction forces, so they win the tug of war with cells on the softer part. They further show that even cells that do not show durotaxis as single cells can durotax as a collective.

    Article  CAS  PubMed  Google Scholar 

  55. Abercrombie, M. & Heaysman, J. E. Observations on the social behaviour of cells in tissue culture: I. Speed of movement of chick heart fibroblasts in relation to their mutual contacts. Exp. Cell Res. 5, 111–131 (1953).

    CAS  PubMed  Google Scholar 

  56. Carmona-Fontaine, C. et al. Contact inhibition of locomotion in vivo controls neural crest directional migration. Nature 456, 957–961 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Theveneau, E. et al. Chase-and-run between adjacent cell populations promotes directional collective migration. Nat. Cell Biol. 15, 763–772 (2013). In this paper, the authors show the importance of multiple cellular interactions of different cell types for collective cell migration. They study the interactions between neural crest cells and placode cells, an epithelial tissue, identifying a mechanism based on a coupling between chemotaxis and mechanical forces that promotes the correct migration of neural crest cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bahm, I. et al. PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration. Development 144, 2456–2468 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Desai, R. A., Gao, L., Raghavan, S., Liu, W. F. & Chen, C. S. Cell polarity triggered by cell-cell adhesion via E-cadherin. J. Cell Sci. 122, 905–911 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Ouyang, M. et al. N-Cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways. Nat. Commun. 4, 1589 (2013).

    Article  PubMed  CAS  Google Scholar 

  61. Kocgozlu, L. et al. Epithelial cell packing induces distinct modes of cell extrusions. Curr. Biol. 26, 2942–2950 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Park, J. A., Atia, L., Mitchel, J. A., Fredberg, J. J. & Butler, J. P. Collective migration and cell jamming in asthma, cancer and development. J. Cell Sci. 129, 3375–3383 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Garcia, S. et al. Physics of active jamming during collective cellular motion in a monolayer. Proc. Natl Acad. Sci. USA 112, 15314–15319 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Deforet, M., Hakim, V., Yevick, H., Duclos, G. & Silberzan, P. Emergence of collective modes and tri-dimensional structures from epithelial confinement. Nat. Commun. 5, 3747 (2014). This paper shows that cellular confinement of epithelial cells in vitro can lead to spontaneous modes of collective oscillatory movements. A simple mathematical model, in which cells are described as persistent random walkers that adapt their motion to their neighbours, with an additional term that mimics cell adhesion, captures the essential characteristics of these oscillatory modes.

    Article  CAS  PubMed  Google Scholar 

  65. Sadati, M., Qazvini, N. T., Krishnan, R., Park, C. Y. & Fredberg, J. J. Collective migration and cell jamming. Differentiation 86, 121–125 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tambe, D. T. et al. Collective cell guidance by cooperative intercellular forces. Nat. Mater. 10, 469–475 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bi, D. P., Lopez, J. H., Schwarz, J. M. & Manning, M. L. A density-independent rigidity transition in biological tissues. Nat. Phys. 11, 1074–1079 (2015).

    Article  CAS  Google Scholar 

  68. Reffay, M. et al. Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells. Nat. Cell Biol. 16, 217–223 (2014). In this paper, the authors analyse the mechanical role of leader cells during collective cell migration. They measure the forces exerted by finger-like structures composed of multiple cells at the migrating front and correlate the mechanical forces with RHOA activity.

    Article  CAS  PubMed  Google Scholar 

  69. Trepat, X. et al. Physical forces during collective cell migration. Nat. Phys. 5, 426–430 (2009).

    Article  CAS  Google Scholar 

  70. du Roure, O. et al. Force mapping in epithelial cell migration. Proc. Natl Acad. Sci. USA 102, 2390–2395 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jacinto, A., Martinez-Arias, A. & Martin, P. Mechanisms of epithelial fusion and repair. Nat. Cell Biol. 3, E117–E123 (2001).

    Article  CAS  PubMed  Google Scholar 

  72. Ravasio, A. et al. Gap geometry dictates epithelial closure efficiency. Nat. Commun. 6, 7683 (2015). To analyse epithelial gap closure, the authors experimentally implemented microscopic gaps of defined geometries and curvatures into confluent epithelial sheets. Their study clarifies the roles of two gap-closing mechanisms — cell migration and actomyosin-based contractile cable dynamics — and describes how the relative contributions of the two mechanisms are affected by gap geometry.

  73. Nier, V. et al. Inference of internal stress in a cell monolayer. Biophys. J. 110, 1625–1635 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hutson, M. S. et al. Forces for morphogenesis investigated with laser microsurgery and quantitative modeling. Science 300, 145–149 (2003).

    Article  CAS  PubMed  Google Scholar 

  75. Serra-Picamal, X. et al. Mechanical waves during tissue expansion. Nat. Phys. 8, 628–634 (2012).

    Article  CAS  Google Scholar 

  76. Nelson, C. M. et al. Emergent patterns of growth controlled by multicellular form and mechanics. Proc. Natl Acad. Sci. USA 102, 11594–11599 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Warmflash, A., Sorre, B., Etoc, F., Siggia, E. D. & Brivanlou, A. H. A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. Nat. Methods 11, 847–854 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Buckley, C. D. et al. The minimal cadherin-catenin complex binds to actin filaments under force. Science 346, 1254211 (2014). In this paper, the authors use single molecule assays to analyse cadherin–α-catenin complexes and their interaction with actin filaments under force. They show that tension is required to stabilize a linkage between the cadherin–catenin complex and actin filaments, and they clarify how the cadherin–catenin complex could interact directly with the actin cytoskeleton in cells.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Yonemura, S., Wada, Y., Watanabe, T., Nagafuchi, A. & Shibata, M. α-Catenin as a tension transducer that induces adherens junction development. Nat. Cell Biol. 12, 533–542 (2010).

    Article  CAS  PubMed  Google Scholar 

  80. Ladoux, B. et al. Strength dependence of cadherin-mediated adhesions. Biophys. J. 98, 534–542 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Blanchoin, L., Boujemaa-Paterski, R., Sykes, C. & Plastino, J. Actin dynamics, architecture, and mechanics in cell motility. Physiol. Rev. 94, 235–263 (2014).

    Article  CAS  PubMed  Google Scholar 

  82. Plotnikov, S. V., Pasapera, A. M., Sabass, B. & Waterman, C. M. Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration. Cell 151, 1513–1527 (2012).

    Article  CAS  PubMed  Google Scholar 

  83. Gupta, M. et al. Adaptive rheology and ordering of cell cytoskeleton govern matrix rigidity sensing. Nat. Commun. 6, 7525 (2015).

    Article  CAS  PubMed  Google Scholar 

  84. Gudipaty, S. A. et al. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature 543, 118–121 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kaliman, S., Jayachandran, C., Rehfeldt, F. & Smith, A. S. Novel growth regime of MDCK II model tissues on soft substrates. Biophys. J. 106, L25–28 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. de Rooij, J., Kerstens, A., Danuser, G., Schwartz, M. A. & Waterman-Storer, C. M. Integrin-dependent actomyosin contraction regulates epithelial cell scattering. J. Cell Biol. 171, 153–164 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mertz, A. F. et al. Cadherin-based intercellular adhesions organize epithelial cell-matrix traction forces. Proc. Natl Acad. Sci. USA 110, 842–847 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. Maki, K. et al. Mechano-adaptive sensory mechanism of α-catenin under tension. Sci. Rep. 6, 24878 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Yao, M. et al. Force-dependent conformational switch of α-catenin controls vinculin binding. Nat. Commun. 5, 4525 (2014).

    Article  CAS  PubMed  Google Scholar 

  90. Barry, A. K. et al. α-Catenin cytomechanics — role in cadherin-dependent adhesion and mechanotransduction. J. Cell Sci. 127, 1779–1791 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Acharya, B. R. et al. Mammalian diaphanous 1 mediates a pathway for E-cadherin to stabilize epithelial barriers through junctional contractility. Cell Rep. 18, 2854–2867 (2017).

    Article  CAS  PubMed  Google Scholar 

  92. Kim, T. J. et al. Dynamic visualization of α-catenin reveals rapid, reversible conformation switching between tension states. Curr. Biol. 25, 218–224 (2015).

    Article  CAS  PubMed  Google Scholar 

  93. Mège, R. M. & Ishiyama, N. Integration of cadherin adhesion and cytoskeleton at adherens junctions. Cold Spring Harb. Perspect. Biol. 9, a028738 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Borghi, N. et al. E-Cadherin is under constitutive actomyosin-generated tension that is increased at cell-cell contacts upon externally applied stretch. Proc. Natl Acad. Sci. USA 109, 12568–12573 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bertocchi, C. et al. Nanoscale architecture of cadherin-based cell adhesions. Nat. Cell Biol. 19, 28–37 (2017).

    Article  CAS  PubMed  Google Scholar 

  96. Vasioukhin, V., Bauer, C., Yin, M. & Fuchs, E. Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 100, 209–219 (2000).

    Article  CAS  PubMed  Google Scholar 

  97. Twiss, F. et al. Vinculin-dependent cadherin mechanosensing regulates efficient epithelial barrier formation. Biol. Open 1, 1128–1140 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Causeret, M., Taulet, N., Comunale, F., Favard, C. & Gauthier-Rouviere, C. N-Cadherin association with lipid rafts regulates its dynamic assembly at cell-cell junctions in C2C12 myoblasts. Mol. Biol. Cell 16, 2168–2180 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. le Duc, Q. et al. 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, 1107–1115 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ladoux, B., Nelson, W. J., Yan, J. & Mège, R. M. The mechanotransduction machinery at work at adherens junctions. Integr. Biol. 1109–1119 (2015).

  101. Choi, W. et al. Remodeling the zonula adherens in response to tension and the role of afadin in this response. J. Cell Biol. 213, 243–260 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Mason, F. M., Xie, S., Vasquez, C. G., Tworoger, M. & Martin, A. C. RhoA GTPase inhibition organizes contraction during epithelial morphogenesis. J. Cell Biol. 214, 603–617 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Martin, A. C. & Goldstein, B. Apical constriction: themes and variations on a cellular mechanism driving morphogenesis. Development 141, 1987–1998 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Acharya, B. R. & Yap, A. S. Pli selon pli: mechanochemical feedback and the morphogenetic role of contractility at cadherin cell-cell junctions. Curr. Top. Dev. Biol. 117, 631–646 (2016).

    Article  PubMed  Google Scholar 

  105. Priya, R. & Yap, A. S. Active tension: the role of cadherin adhesion and signaling in generating junctional contractility. Curr. Top. Dev. Biol. 112, 65–102 (2015).

    Article  CAS  PubMed  Google Scholar 

  106. Jodoin, J. N. et al. Stable force balance between epithelial cells arises from F-actin turnover. Dev. Cell 35, 685–697 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Begnaud, S., Chen, T., Delacour, D., Mège, R. M. & Ladoux, B. Mechanics of epithelial tissues during gap closure. Curr. Opin. Cell Biol. 42, 52–62 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Lawson, C. D. & Burridge, K. The on-off relationship of Rho and Rac during integrin-mediated adhesion and cell migration. Small GTPases 5, e27958 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Omelchenko, T. et al. β-Pix directs collective migration of anterior visceral endoderm cells in the early mouse embryo. Genes Dev. 28, 2764–2777 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Cai, D. et al. Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration. Cell 157, 1146–1159 (2014). This paper illustrates the importance of E-cadherin during border cell migration in D. melanogaster , showing that E-cadherin adhesions maintain the cohesion and polarity of the group through mechanical feedback.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hayer, A. et al. Engulfed cadherin fingers are polarized junctional structures between collectively migrating endothelial cells. Nat. Cell Biol. 18, 1311–1323 (2016). This paper shows the formation of cadherin fingers along moving endothelial cell monolayers, which are cadherin-rich protrusions that are extended from leading migrating cells and engulfed by follower cells to guide collective migration.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Dorland, Y. L. et al. The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions. Nat. Commun. 7, 12210 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Davies, P. F. Flow-mediated endothelial mechanotransduction. Physiol Rev. 75, 519–560 (1995).

    Article  CAS  PubMed  Google Scholar 

  114. Solon, J., Kaya-Copur, A., Colombelli, J. & Brunner, D. Pulsed forces timed by a ratchet-like mechanism drive directed tissue movement during dorsal closure. Cell 137, 1331–1342 (2009).

    Article  PubMed  Google Scholar 

  115. Segerer, F. J., Thuroff, F., Piera Alberola, A., Frey, E. & Radler, J. O. Emergence and persistence of collective cell migration on small circular micropatterns. Phys. Rev. Lett. 114, 228102 (2015).

    Article  PubMed  CAS  Google Scholar 

  116. Rolli, C. G. et al. Switchable adhesive substrates: revealing geometry dependence in collective cell behavior. Biomaterials 33, 2409–2418 (2012).

    Article  CAS  PubMed  Google Scholar 

  117. Friedl, P., Locker, J., Sahai, E. & Segall, J. E. Classifying collective cancer cell invasion. Nat. Cell Biol. 14, 777–783 (2012).

    Article  PubMed  CAS  Google Scholar 

  118. Doxzen, K. et al. Guidance of collective cell migration by substrate geometry. Integr. Biol. 5, 1026–1035 (2013).

    Article  CAS  Google Scholar 

  119. Tanner, K., Mori, H., Mroue, R., Bruni-Cardoso, A. & Bissell, M. J. Coherent angular motion in the establishment of multicellular architecture of glandular tissues. Proc. Natl Acad. Sci. USA 109, 1973–1978 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Haigo, S. L. & Bilder, D. Global tissue revolutions in a morphogenetic movement controlling elongation. Science 331, 1071–1074 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Notbohm, J. et al. Cellular contraction and polarization drive collective cellular motion. Biophys. J. 110, 2729–2738 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Grasso, S., Hernández, J. A. & Chifflet, S. Roles of wound geometry, wound size, and extracellular matrix in the healing response of bovine corneal endothelial cells in culture. Am. J. Physiol. Cell Physiol. 293, C1327–C1337 (2007).

    Article  CAS  PubMed  Google Scholar 

  123. Klarlund, J. K. Dual modes of motility at the leading edge of migrating epithelial cell sheets. Proc. Natl Acad. Sci. USA 109, 15799–15804 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Rausch, S. et al. Polarizing cytoskeletal tension to induce leader cell formation during collective cell migration. Biointerphases 8, 32 (2013).

    Article  PubMed  CAS  Google Scholar 

  125. Watt, F. M. & Fujiwara, H. Cell-extracellular matrix interactions in normal and diseased skin. Cold Spring Harb. Perspect. Biol. 3, a005124 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Goodwin, K. et al. Basal cell-extracellular matrix adhesion regulates force transmission during tissue morphogenesis. Dev. Cell 39, 611–625 (2016).

    Article  CAS  PubMed  Google Scholar 

  127. Paszek, M. J. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241–254 (2005).

    Article  CAS  PubMed  Google Scholar 

  128. Pelham, R. J. & Wang, Y. L. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl Acad. Sci. USA 94, 13661–13665 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Koser, D. E. et al. Mechanosensing is critical for axon growth in the developing brain. Nat. Neurosci. 19, 1592–1598 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Reinhart-King, C. A., Dembo, M. & Hammer, D. A. Cell-cell mechanical communication through compliant substrates. Biophys. J. 95, 6044–6051 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Angelini, T. E., Hannezo, E., Trepat, X., Fredberg, J. J. & Weitz, D. A. Cell migration driven by cooperative substrate deformation patterns. Phys. Rev. Lett. (2010).

  132. Saez, A., Buguin, A., Silberzan, P. & Ladoux, B. Is the mechanical activity of epithelial cells controlled by deformations or forces? Biophys. J. 89, L52–L54 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Saez, A., Ghibaudo, M., Buguin, A., Silberzan, P. & Ladoux, B. Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates. Proc. Natl Acad. Sci. USA 104, 8281–8286 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Guo, W. H., Frey, M. T., Burnham, N. A. & Wang, Y. L. Substrate rigidity regulates the formation and maintenance of tissues. Biophys. J. 90, 2213–2220 (2006).

    Article  CAS  PubMed  Google Scholar 

  135. Douezan, S., Dumond, J. & Brochard-Wyart, F. Wetting transitions of cellular aggregates induced by substrate rigidity. Soft Matter 8, 4578–4583 (2012).

    Article  CAS  Google Scholar 

  136. Raab, M. et al. Crawling from soft to stiff matrix polarizes the cytoskeleton and phosphoregulates myosin-II heavy chain. J. Cell Biol. 199, 669–683 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Williams, C. M., Engler, A. J., Slone, R. D., Galante, L. L. & Schwarzbauer, J. E. Fibronectin expression modulates mammary epithelial cell proliferation during acinar differentiation. Cancer Res. 68, 3185–3192 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C. & Brown, R. A. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol. 3, 349–363 (2002).

    Article  CAS  PubMed  Google Scholar 

  139. Chao, C. Y. et al. In vivo and ex vivo approaches to studying the biomechanical properties of healing wounds in rat skin. J. Biomechan. Engineer. 135, 101009–101008 (2013).

    Article  Google Scholar 

  140. Levental, K. R. et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139, 891–906 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Odenthal, J., Takes, R. & Friedl, P. Plasticity of tumor cell invasion: governance by growth factors and cytokines. Carcinogenesis 37, 1117–1128 (2016).

    CAS  PubMed  Google Scholar 

  142. Takai, Y., Miyoshi, J., Ikeda, W. & Ogita, H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat. Rev. Mol. Cell Biol. 9, 603–615 (2008).

    Article  CAS  PubMed  Google Scholar 

  143. Wu, Y., Kanchanawong, P. & Zaidel-Bar, R. Actin-delimited adhesion-independent clustering of E-cadherin forms the nanoscale building blocks of adherens junctions. Dev. Cell 32, 139–154 (2015).

    Article  CAS  PubMed  Google Scholar 

  144. Truong Quang, B. A., Mani, M., Markova, O., Lecuit, T. & Lenne, P. F. Principles of E-cadherin supramolecular organization in vivo. Curr. Biol. 23, 2197–2207 (2013).

    Article  CAS  PubMed  Google Scholar 

  145. Hong, S., Troyanovsky, R. B. & Troyanovsky, S. M. Binding to F-actin guides cadherin cluster assembly, stability, and movement. J. Cell Biol. 201, 131–143 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Strale, P. O. et al. The formation of ordered nanoclusters controls cadherin anchoring to actin and cell-cell contact fluidity. J. Cell Biol. 210, 333–346 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Wu, Y., Vendome, J., Shapiro, L., Ben-Shaul, A. & Honig, B. Transforming binding affinities from three dimensions to two with application to cadherin clustering. Nature 475, 510–513 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Harrison, O. J. et al. The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins. Structure 19, 244–256 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Thomas, W. A. et al. α-Catenin and vinculin cooperate to promote high E-cadherin-based adhesion strength. J. Biol. Chem. 288, 4957–4969 (2013).

    Article  CAS  PubMed  Google Scholar 

  150. Niewiadomska, P., Godt, D. & Tepass, U. DE-cadherin is required for intercellular motility during Drosophila oogenesis. J. Cell Biol. 144, 533–547 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Bruce, A. E. Zebrafish epiboly: spreading thin over the yolk. Dev. Dyn. 245, 244–258 (2016).

    Article  CAS  PubMed  Google Scholar 

  152. Harrison, O. J. et al. Nectin ectodomain structures reveal a canonical adhesive interface. Nat. Struct. Mol. Biol. 19, 906–915 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Troyanovsky, R. B., Indra, I., Chen, C. S., Hong, S. & Troyanovsky, S. M. Cadherin controls nectin recruitment into adherens junctions by remodeling the actin cytoskeleton. J. Cell Sci. 128, 140–149 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Honda, T. et al. Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion. Genes Cells 8, 51–63 (2003).

    Article  CAS  PubMed  Google Scholar 

  155. Nikolic, D. L., Boettiger, A. N., Bar-Sagi, D., Carbeck, J. D. & Shvartsman, S. Y. Role of boundary conditions in an experimental model of epithelial wound healing. Am. J. Physiol. Cell Physiol. 291, C68–C75 (2006).

    Article  CAS  PubMed  Google Scholar 

  156. Murrell, M., Kamm, R. & Matsudaira, P. Tension, free space, and cell damage in a microfluidic wound healing assay. PLoS ONE 6, e24283 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. van der Meer, A. D., Vermeul, K., Poot, A. A., Feijen, J. & Vermes, I. A microfluidic wound-healing assay for quantifying endothelial cell migration. Am. J. Physiol. Heart Circ. Physiol. 298, H719–H725 (2010).

    Article  CAS  PubMed  Google Scholar 

  158. Gul, I. S., Hulpiau, P., Saeys, Y. & van Roy, F. Evolution and diversity of cadherins and catenins. Exp. Cell Res. 358, 3–9 (2017).

    Article  CAS  PubMed  Google Scholar 

  159. van Roy, F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat. Rev. Cancer 14, 121–134 (2014).

    Article  CAS  PubMed  Google Scholar 

  160. Plutoni, C. et al. P-Cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces. J. Cell Biol. 212, 199–217 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Chu, Y. S. et al. Prototypical type I E-cadherin and type II cadherin-7 mediate very distinct adhesiveness through their extracellular domains. J. Biol. Chem. 281, 2901–2910 (2006).

    Article  CAS  PubMed  Google Scholar 

  162. Labernadie, A. et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat. Cell Biol. 19, 224–237 (2017). This paper shows that cancer-associated fibroblasts (CAFs) form heterotypic E-cadherin–N-cadherin contacts with tumour cells, exerting a physical force on cancer cells that enables their collective invasion.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Sawyer, J. K. et al. A contractile actomyosin network linked to adherens junctions by Canoe/afadin helps drive convergent extension. Mol. Biol. Cell 22, 2491–2508 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Sawyer, J. K., Harris, N. J., Slep, K. C., Gaul, U. & Peifer, M. The Drosophila afadin homologue Canoe regulates linkage of the actin cytoskeleton to adherens junctions during apical constriction. J. Cell Biol. 186, 57–73 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Mandai, K. et al. Afadin: a novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction. J. Cell Biol. 139, 517–528 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Ikeda, W. et al. Afadin: a key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J. Cell Biol. 146, 1117–1132 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Zhadanov, A. B. et al. Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell junctions and cell polarity during mouse development. Curr. Biol. 9, 880–888 (1999).

    Article  CAS  PubMed  Google Scholar 

  168. Weber, G. F., Bjerke, M. A. & DeSimone, D. W. A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration. Dev. Cell 22, 104–115 (2012).

    Article  CAS  PubMed  Google Scholar 

  169. Mayer, M., Depken, M., Bois, J. S., Julicher, F. & Grill, S. W. Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows. Nature 467, 617–621 (2010).

    Article  CAS  PubMed  Google Scholar 

  170. Dembo, M., Oliver, T., Ishihara, A. & Jacobson, K. Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys. J. 70, 2008–2022 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Tan, J. L. et al. Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl Acad. Sci. USA 100, 1484–1489 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Yamaguchi, N., Mizutani, T., Kawabata, K. & Haga, H. Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin β1 and PI3K. Sci. Rep. 5, 7656 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Osmani, N., Peglion, F., Chavrier, P. & Etienne-Manneville, S. Cdc42 localization and cell polarity depend on membrane traffic. J. Cell Biol. 191, 1261–1269 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank all members of the Institut Jacques Monod (IJM) and Mechanobiology Institute (MBI) teams and T. Chen, D. Delacour, P. Marcq, T. B. Saw and R. Voituriez for helpful discussions and/or critical reading of the manuscript. The authors also thank D. Pitta de Araujo, C. X. Wong and S. Wolf from MBI Science Communication Core for their substantial help with the illustrations. The authors receive financial support from the National University of Singapore/Université Sorbonne Paris Cité (NUS/USPC) and Le Projet International de Coopération Scientifique (PICS) Centre National de la Recherche Scientifique (CNRS) programmes, the European Research Council under the European Union's Seventh Framework Program (FP7/2007–2013)/European Research Council (ERC) (grant agreement number 617233), the LABEX 'Who am I?' and the Mechanobiology Institute (Singapore).

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Authors and Affiliations

  1. Institut Jacques Monod (IJM), Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7592 and Université Paris Diderot, Paris, 72505, France

    Benoit Ladoux & René-Marc Mège

  2. Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore, 117411

    Benoit Ladoux

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  1. Benoit Ladoux
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The authors contributed equally to all aspects of the article (researching data for the article, substantial contribution to discussion of content and writing, review and editing of manuscript before submission).

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Supplementary information

Supplementary information S1 (box)

Examples of morphogenetic processes involving collective cell migration in vivo (PDF 404 kb)

Supplementary information S2 (box)

Physical models for collective cell behaviours. (PDF 359 kb)

Supplementary information S3 (box)

Mechanocoupling by tight junctions. (PDF 170 kb)

Supplementary information S4 (box)

Mechanocoupling by desmosomes and intermediary filaments. (PDF 176 kb)

PowerPoint slides

Glossary

Border cells

In Drosophila melanogaster, a cluster of six to eight migratory cells migrating in the egg chamber from the follicular epithelium towards the oocyte.

Lateral line

A system of sense organs found in fish, allowing the detection of movement, vibration and pressure gradients in the water.

Traction forces

Forces exerted by cells on their underlying surfaces during adhesion or migration.

Velocity fields

Maps of the flows of tissues by measuring the displacement field of natural tracers inside the tissues between successive images.

Reynolds number

Dimensionless quantity used in hydrodynamics that represent the ratio between inertial forces and viscous forces. Laminar flows occur at low Reynolds number, whereas turbulent flows appear at high Reynolds number.

Cell extrusion

An expulsion of apoptotic, non-apoptotic or transformed cells from a cell monolayer (apically or basally).

Cryptic lamellipodia

Short lamellipodia forming under neighbouring cells in a migrating monolayer.

Neural crest cells

In vertebrates, a group of migrating cells that arises from the border between the neural plate and the non-neural ectoderm.

Confluence

In cell culture, the state in which 100% of the surface is covered by cells; also called 100% confluence.

Cortical tension

The force per unit length exerted on a part of the cortex, which is a thin layer mainly composed of actin-based proteins and myosin attached to the cell membrane, by the network around it.

Focal adhesions

Integrin-mediated adhesion structures formed at the cell–ECM interface, at the anchorage points of stress fibres.

Optical tweezers

Highly focused laser beams that attract small objects to the centre of the beam.

Stress

The force per unit area.

Strain

A measure of deformation representing the length change in a body relative to a reference length.

Shear

Local stresses exerted tangentially to a defined surface.

Normal stress

Forces perpendicular to a defined surface, such as a cell–cell interface.

Catch bond

A noncovalent bond that shows an increased lifetime with increasing amounts of tensile force applied to the bond.

Förster resonance energy transfer

(FRET). When applied to optical microscopy, a method allowing the determination of the distance (or dynamic changes in the proximity) between two fluorescent molecules within several nanometres.

Cancer-associated fibroblasts

(CAFs). Stromal fibroblasts closely associated with primary tumour cells and participating in the neoplastic process.

Hippo pathway

Also known as the Salvador–Warts–Hippo pathway, this pathway controls organ size in animals through the regulation of cell proliferation and apoptosis.

ERM family

A protein family that is named for three closely related proteins: ezrin, radixin and moesin.

BAR domain

A highly conserved protein dimerization domain that occurs in many proteins involved in cellular membrane dynamics. The BAR domain is banana-shaped, binds to membranes and is capable of sensing membrane curvature by binding preferentially to curved membranes.

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Ladoux, B., Mège, RM. Mechanobiology of collective cell behaviours. Nat Rev Mol Cell Biol 18, 743–757 (2017). https://doi.org/10.1038/nrm.2017.98

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