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Mesoscale physical principles of collective cell organization

Nature Physics volume 14, pages 671–682 (2018)Cite this article

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Abstract

We review recent evidence showing that cell and tissue dynamics are governed by mesoscale physical principles. These principles can be understood in terms of simple state diagrams in which control variables include force, density, shape, adhesion and self-propulsion. An appropriate combination of these physical quantities gives rise to emergent phenomena such as cell jamming, topological defects and underdamped waves. Mesoscale physical properties of cell assemblies are found to precede and instruct biological functions such as cell division, extrusion, invasion and gradient sensing. These properties are related to properties of biomolecules, but cannot be predicted from biochemical principles. Thus, biological function is governed by emergent mesoscale states that can be predicted by a simple set of physical properties.

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Fig. 1: Subcellular determinants of cell dynamics.
Fig. 2: Examples of emergent phenomena in cell monolayers.

adapted from ref. 2, Macmillan Publishers Ltd (a); ref. 78, Macmillan Publishers Ltd (b); and ref. 4, AAAS (c)

Fig. 3: State diagrams of cell monolayers.

adapted from ref. 86, RSC, and ref. 87, Macmillan Publishers Ltd (a); and courtesy of R. Cerbino and F. Giavazzi (b,c).

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References

  1. Alberts, B. et al. Molecular Biology of the Cell 6th edn (Garland Science, New York, NY, 2016).

  2. Duclos, G., Erlenkämper, C., Joanny, J.-F. & Silberzan, P. Topological defects in confined populations of spindle-shaped cells. Nat. Phys. 13, 58–62 (2016).

    Google Scholar 

  3. Saw, T. B. et al. Topological defects in epithelia govern cell death and extrusion. Nature 544, 212–216 (2017).

    ADS  Google Scholar 

  4. Sunyer, R. et al. Collective cell durotaxis emerges from long-range intercellular force transmission. Science 353, 1157–1161 (2016).

    ADS  Google Scholar 

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

    ADS  Google Scholar 

  6. Das, T. et al. A molecular mechanotransduction pathway regulates collective migration of epithelial cells. Nat. Cell Biol. 17, 276–287 (2015).

    Google Scholar 

  7. Hogan, B. L. & Kolodziej, P. A. Organogenesis: molecular mechanisms of tubulogenesis. Nat. Rev. Genet. 3, 513–523 (2002).

    Google Scholar 

  8. Bryant, D. M. & Mostov, K. E. From cells to organs: building polarized tissue. Nat. Rev. Mol. Cell Biol. 9, 887–901 (2008).

    Google Scholar 

  9. Kawaguchi, K., Kageyama, R. & Sano, M. Topological defects control collective dynamics in neural progenitor cell cultures. Nature 545, 327–331 (2017).

    ADS  Google Scholar 

  10. Spurlin, J. W. 3rd & Nelson, C. M. Building branched tissue structures: from single cell guidance to coordinated construction. Philos. Trans. R. Soc. B. 372, 20150527 (2017).

    Google Scholar 

  11. Laurent, J. et al. Convergence of microengineering and cellular self-organization towards functional tissue manufacturing. Nat. Biomed. Eng. 1, 939–956 (2017).

    Google Scholar 

  12. Ladoux, B. & Mege, R. M. Mechanobiology of collective cell behaviours. Nat. Rev. Mol. Cell Biol. 18, 743–757 (2017).

    Google Scholar 

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

    ADS  Google Scholar 

  14. Chen, B. C. et al. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346, 1257998 (2014).

    Google Scholar 

  15. Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003).

    Google Scholar 

  16. Loisel, T. P., Boujemaa, R., Pantaloni, D. & Carlier, M. F. Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature 401, 613–616 (1999).

    ADS  Google Scholar 

  17. Finer, J. T., Simmons, R. M. & Spudich, J. A. Single myosin molecule mechanics: piconewton forces and nanometre steps. Nature 368, 113–119 (1994).

    ADS  Google Scholar 

  18. Newell-Litwa, K. A., Horwitz, R. & Lamers, M. L. Non-muscle myosin II in disease: mechanisms and therapeutic opportunities. Dis. Models Mech. 8, 1495–1515 (2015).

    Google Scholar 

  19. Mitchison, T. J., Charras, G. T. & Mahadevan, L. Implications of a poroelastic cytoplasm for the dynamics of animal cell shape. Semin. Cell Dev. Biol. 19, 215–223 (2008).

    Google Scholar 

  20. McDonald, N. A. & Gould, K. L. Linking up at the BAR: oligomerization and F-BAR protein function. Cell Cycle 15, 1977–1985 (2016).

    Google Scholar 

  21. Kruse, K., Joanny, J. F., Julicher, F., Prost, J. & Sekimoto, K. Generic theory of active polar gels: a paradigm for cytoskeletal dynamics. Eur. Phys. J. E 16, 5–16 (2005).

    Google Scholar 

  22. Jülicher, F. & Prost, J. Spontaneous oscillations of collective molecular motors. Phys. Rev. Lett. 78, 4510–4513 (1997).

    ADS  Google Scholar 

  23. Joanny, J. F. & Prost, J. Active gels as a description of the actin-myosin cytoskeleton. HFSP J. 3, 94–104 (2009).

    Google Scholar 

  24. Alvarado, J., Sheinman, M., Sharma, A., MacKintosh, F. C. & Koenderink, G. H. Force percolation of contractile active gels. Soft Matter 13, 5624–5644 (2017).

    ADS  Google Scholar 

  25. Roca-Cusachs, P., Conte, V. & Trepat, X. Quantifying forces in cell biology. Nat. Cell Biol. 19, 742–751 (2017).

    Google Scholar 

  26. Fabry, B. et al. Scaling the microrheology of living cells. Phys. Rev. Lett. 87, 148102 (2001).

    ADS  Google Scholar 

  27. Alcaraz, J. et al. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys. J. 84, 2071–2079 (2003).

    ADS  Google Scholar 

  28. Sanghvi-Shah, R. & Weber, G. F. Intermediate filaments at the junction of mechanotransduction, migration, and development. Front. Cell Dev. Biol. 5, 81 (2017).

    Google Scholar 

  29. Goldmann, W. H. Intermediate filaments and cellular mechanics. Cell Biol. Int. 42, 132–138 (2017).

    Google Scholar 

  30. Block, J. et al. Nonlinear loading-rate-dependent force response of individual vimentin intermediate filaments to applied strain. Phys. Rev. Lett. 118, 048101 (2017).

    ADS  Google Scholar 

  31. Beil, M. et al. Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Nat. Cell Biol. 5, 803–811 (2003).

    Google Scholar 

  32. Roostalu, J. & Surrey, T. Microtubule nucleation: beyond the template. Nat. Rev. Mol. Cell Biol. 18, 702–710 (2017).

    Google Scholar 

  33. Brangwynne, C. P. et al. Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement. J. Cell Biol. 173, 733–741 (2006).

    Google Scholar 

  34. Muroyama, A. & Lechler, T. Microtubule organization, dynamics and functions in differentiated cells. Development 144, 3012–3021 (2017).

    Google Scholar 

  35. Haga, R. B. & Ridley, A. J. Rho GTPases: Regulation and roles in cancer cell biology. Small GTPases 7, 207–221 (2016).

    Google Scholar 

  36. Pfeffer, S. R. Rab GTPases: master regulators that establish the secretory and endocytic pathways. Mol. Biol. Cell 28, 712–715 (2017).

    Google Scholar 

  37. Physical Sciences - Oncology Centers Network. A physical sciences network characterization of non-tumorigenic and metastatic cells. Sci. Rep. 3, 1449 (2013).

    Google Scholar 

  38. Lee, J. S. et al. Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration. Biophys. J. 93, 2542–2552 (2007).

    ADS  Google Scholar 

  39. Guilak, F., Tedrow, J. R. & Burgkart, R. Viscoelastic properties of the cell nucleus. Biochem. Biophys. Res. Commun. 269, 781–786 (2000).

    Google Scholar 

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

    Google Scholar 

  41. Ladoux, B., Nelson, W. J., Yan, J. & Mege, R. M. The mechanotransduction machinery at work at adherens junctions. Integr. Biol. 7, 1109–1119 (2015).

    Google Scholar 

  42. Panorchan, P. et al. Single-molecule analysis of cadherin-mediated cell–cell adhesion. J. Cell Sci. 119, 66–74 (2006).

    Google Scholar 

  43. Shawky, J. H. & Davidson, L. A. Tissue mechanics and adhesion during embryo development. Dev. Biol. 401, 152–164 (2015).

    Google Scholar 

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

    Google Scholar 

  45. Hatzfeld, M., Keil, R. & Magin, T. M. Desmosomes and intermediate filaments: their consequences for tissue mechanics. Cold Spring Harb. Perspect. Biol. 9, a029157 (2017).

    Google Scholar 

  46. Storm, C., Pastore, J. J., MacKintosh, F. C., Lubensky, T. C. & Janmey, P. A. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005).

    ADS  Google Scholar 

  47. Chang, A. C. et al. Single molecule force measurements in living cells reveal a minimally tensioned integrin state. ACS Nano 10, 10745–10752 (2016).

    Google Scholar 

  48. Balaban, N. Q. et al. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3, 466–472 (2001).

    Google Scholar 

  49. Winograd-Katz, S. E., Fassler, R., Geiger, B. & Legate, K. R. The integrin adhesome: from genes and proteins to human disease. Nat. Rev. Mol. Cell Biol. 15, 273–288 (2014).

    Google Scholar 

  50. Yao, M. et al. Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. Sci. Rep. 4, 4610 (2014).

    Google Scholar 

  51. Sun, Z., Guo, S. S. & Fassler, R. Integrin-mediated mechanotransduction. J. Cell Biol. 215, 445–456 (2016).

    Google Scholar 

  52. Dembo, M. & Wang, Y. L. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys. J. 76, 2307–2316 (1999).

    ADS  Google Scholar 

  53. Bastounis, E. et al. Both contractile axial and lateral traction force dynamics drive amoeboid cell motility. J. Cell Biol. 204, 1045–1061 (2014).

    Google Scholar 

  54. Murrell, M. P. et al. Liposome adhesion generates traction stress. Nat. Phys. 10, 163–169 (2014).

    Google Scholar 

  55. Schwarz, U. S. & Soine, J. R. Traction force microscopy on soft elastic substrates: A guide to recent computational advances. Biochim. Biophys. Acta 1853, 3095–3104 (2015).

    Google Scholar 

  56. Chan, C. E. & Odde, D. J. Traction dynamics of filopodia on compliant substrates. Science 322, 1687–1691 (2008).

    ADS  Google Scholar 

  57. Elosegui-Artola, A. et al. Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat. Cell Biol. 18, 540–548 (2016).

    Google Scholar 

  58. Maître, J.-L. et al. Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells. Science 338, 253–256 (2012).

    ADS  Google Scholar 

  59. Maruthamuthu, V., Sabass, B., Schwarz, U. S. & Gardel, M. L. Cell–ECM traction force modulates endogenous tension at cell–cell contacts. Proc. Natl Acad. Sci. USA 108, 4708–4713 (2011).

    ADS  Google Scholar 

  60. Tozluoglu, M. et al. Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions. Nat. Cell Biol. 15, 751–762 (2013).

    Google Scholar 

  61. Tozluoglu, M., Mao, Y., Bates, P. A. & Sahai, E. Cost-benefit analysis of the mechanisms that enable migrating cells to sustain motility upon changes in matrix environments. J. R. Soc. Interface 12, 1355 (2015).

    Google Scholar 

  62. Bergert, M. et al. Force transmission during adhesion-independent migration. Nat. Cell Biol. 17, 524–529 (2015).

    Google Scholar 

  63. Yeh, Y. T. et al. Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis. Proc. Natl Acad. Sci. USA 115, 133–138 (2018).

    Google Scholar 

  64. del Rio, A. et al. Stretching single talin rod molecules activates vinculin binding. Science 323, 638–641 (2009).

    ADS  Google Scholar 

  65. Elosegui-Artola, A. et al. Rigidity sensing and adaptation through regulation of integrin types. Nat. Mater. 13, 631–637 (2014).

    ADS  Google Scholar 

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

    Google Scholar 

  67. 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).

    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).

    Google Scholar 

  69. 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. Nat. Commun. 5, 5720 (2014).

    ADS  Google Scholar 

  70. Marel, A. K. et al. Flow and diffusion in channel-guided cell migration. Biophys. J. 107, 1054–1064 (2014).

    ADS  Google Scholar 

  71. Zaritsky, A. et al. Seeds of locally aligned motion and stress coordinate a collective cell migration. Biophys. J. 109, 2492–2500 (2015).

    ADS  Google Scholar 

  72. Theveneau, E. et al. Collective chemotaxis requires contact-dependent cell polarity. Dev. Cell 19, 39–53 (2010).

    Google Scholar 

  73. Trepat, X. & Fredberg, J. J. Plithotaxis and emergent dynamics in collective cellular migration. Trends Cell Biol. 21, 638–646 (2011).

    Google Scholar 

  74. Malet-Engra, G. et al. Collective cell motility promotes chemotactic prowess and resistance to chemorepulsion. Curr. Biol. 25, 242–250 (2015).

    Google Scholar 

  75. Yang, T. D., Kim, H., Yoon, C., Baek, S.-K. & Lee, K. J. Collective pulsatile expansion and swirls in proliferating tumor tissue. New J. Phys. 18, 103032 (2016).

    ADS  Google Scholar 

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

    ADS  Google Scholar 

  77. Deforet, M., Hakim, V., Yevick, H. G., Duclos, G. & Silberzan, P. Emergence of collective modes and tri-dimensional structures from epithelial confinement. Nat. Commun. 5, 3747 (2014).

    ADS  Google Scholar 

  78. Rodriguez-Franco, P. et al. Long-lived force patterns and deformation waves at repulsive epithelial boundaries. Nat. Mater. 16, 1029–1037 (2017).

    ADS  Google Scholar 

  79. Tlili, S. et al. Collective cell migration without proliferation: density determines cell velocity and wave velocity. R. Soc. Open Sci. 5, 172421 (2018).

    ADS  Google Scholar 

  80. Angelini, T. E. et al. Glass-like dynamics of collective cell migration. Proc. Natl Acad. Sci. USA 108, 4714–4719 (2011).

    ADS  Google Scholar 

  81. Liu, A. J. & Nagel, S. R. Nonlinear dynamics: jamming is not just cool any more. Nature 396, 21–22 (1998).

    ADS  Google Scholar 

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

    Google Scholar 

  83. Farhadifar, R., Roper, J. C., Aigouy, B., Eaton, S. & Julicher, F. The influence of cell mechanics, cell–cell interactions, and proliferation on epithelial packing. Curr. Biol. 17, 2095–2104 (2007).

    Google Scholar 

  84. Merkel, M. & Manning, M. L. A geometrically controlled rigidity transition in a model for confluent 3D tissues. New J. Phys. 20, 022002 (2018).

    ADS  Google Scholar 

  85. Park, J.-A. et al. Unjamming and cell shape in the asthmatic airway epithelium. Nat. Mater. 14, 1040–1048 (2015).

    ADS  Google Scholar 

  86. Malinverno, C. et al. Endocytic reawakening of motility in jammed epithelia. Nat. Mater. 16, 587–596 (2017).

    ADS  Google Scholar 

  87. Giavazzi, F. et al. Flocking transitions in confluent tissues. Soft Matter 14, 3471–3477 (2018).

    ADS  Google Scholar 

  88. Bi, D., Yang, X., Marchetti, M. C. & Manning, M. L. Motility-driven glass and jamming transitions in biological tissues. Phys. Rev. X 6 (2016).

  89. Marchetti, M. C. et al. Hydrodynamics of soft active matter. Rev. Mod. Phys. 85, 1143–1189 (2013).

    ADS  Google Scholar 

  90. Carlsson, J. et al. The influence of oxygen on viability and proliferation in cellular spheroids. Int. J. Radiat. Oncol. Biol. Phys. 5, 2011–2020 (1979).

    Google Scholar 

  91. Conger, A. D. & Ziskin, M. C. Growth of mammalian multicellular tumor spheroids. Cancer Res. 43, 556–560 (1983).

    Google Scholar 

  92. Ewald, A. J. et al. Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium. J. Cell Sci. 125, 2638–2654 (2012).

    Google Scholar 

  93. Charras, G. & Sahai, E. Physical influences of the extracellular environment on cell migration. Nat. Rev. Mol. Cell Biol. 15, 813–824 (2014).

    Google Scholar 

  94. Vedula, S. R. et al. Emerging modes of collective cell migration induced by geometrical constraints. Proc. Natl Acad. Sci. USA 109, 12974–12979 (2012).

    ADS  Google Scholar 

  95. Kabla, A. J. Collective cell migration: leadership, invasion and segregation. J. R. Soc. Interface 9, 3268–3278 (2012).

    Google Scholar 

  96. Wang, H., Lacoche, S., Huang, L., Xue, B. & Muthuswamy, S. K. Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly. Proc. Natl Acad. Sci. USA 110, 163–168 (2013).

    ADS  Google Scholar 

  97. Cetera, M. et al. Epithelial rotation promotes the global alignment of contractile actin bundles during Drosophila egg chamber elongation. Nat. Commun. 5, 5511 (2014).

    ADS  Google Scholar 

  98. Chen, D. Y., Crest, J. & Bilder, D. A cell migration tracking tool supports coupling of tissue rotation to elongation. Cell Rep. 21, 559–569 (2017).

    Google Scholar 

  99. Dolega, M. E. et al. Cell-like pressure sensors reveal increase of mechanical stress towards the core of multicellular spheroids under compression. Nat. Commun. 8, 14056 (2017).

    ADS  Google Scholar 

  100. Stylianopoulos, T. et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc. Natl Acad. Sci. USA 109, 15101–15108 (2012).

    ADS  Google Scholar 

  101. Stylianopoulos, T. The solid mechanics of cancer and strategies for improved therapy. J. Biomech. Eng. 139 (2017).

  102. Stenmark, H. Rab GTPases as coordinators of vesicle traffic. Nat. Rev. Mol. Cell. Biol. 10, 513–525 (2009).

    Google Scholar 

  103. Jaffe, A. B., Kaji, N., Durgan, J. & Hall, A. Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis. J. Cell Biol. 183, 625–633 (2008).

    Google Scholar 

  104. Peaker, M. The effect of raised intramammary pressure on mammary function in the goat in relation to the cessation of lactation. J. Physiol. 301, 415–428 (1980).

    Google Scholar 

  105. Tanner, C., Frambach, D. A. & Misfeldt, D. S. Transepithelial transport in cell culture. A theoretical and experimental analysis of the biophysical properties of domes. Biophys. J. 43, 183–190 (1983).

    Google Scholar 

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

    Google Scholar 

  107. Hutson, M. S., Brodland, G. W., Yang, J. & Viens, D. Cell sorting in three dimensions: topology, fluctuations, and fluidlike instabilities. Phys. Rev. Lett. 101, 148105 (2008).

    ADS  Google Scholar 

  108. Pawlizak, S. et al. Testing the differential adhesion hypothesis across the epithelial−mesenchymal transition. New J. Phys. 17, 083049 (2015).

    ADS  Google Scholar 

  109. Monier, B., Pelissier-Monier, A., Brand, A. H. & Sanson, B. An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos. Nat. Cell Biol. 12, 60–69 (2010).

    Google Scholar 

  110. Gaggioli, C. et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat. Cell Biol. 9, 1392–1400 (2007).

    Google Scholar 

  111. 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).

    Google Scholar 

  112. Theveneau, E. & Linker, C. Leaders in collective migration: are front cells really endowed with a particular set of skills? F1000Res. 6, 1899 (2017).

    Google Scholar 

  113. 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 (2011).

    Google Scholar 

  114. Nelson, C. M. On buckling morphogenesis. J. Biomech. Eng. 138, 021005 (2016).

    Google Scholar 

  115. Hannezo, E. et al. A unifying theory of branching morphogenesis. Cell 171, 242–255.e27 (2017).

    Google Scholar 

  116. Tallinen, T. et al. On the growth and form of cortical convolutions. Nat. Phys. 12, 588–593 (2016).

    Google Scholar 

  117. Hannezo, E., Prost, J. & Joanny, J. F. Instabilities of monolayered epithelia: shape and structure of villi and crypts. Phys. Rev. Lett. 107, 078104 (2011).

    ADS  Google Scholar 

  118. Shyer, A. E. et al. Villification: how the gut gets its villi. Science 342, 212–218 (2013).

    ADS  Google Scholar 

  119. Ewald, A. J., Brenot, A., Duong, M., Chan, B. S. & Werb, Z. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Dev. Cell 14, 570–581 (2008).

    Google Scholar 

  120. Shyer, A. E. et al. Emergent cellular self-organization and mechanosensation initiate follicle pattern in the avian skin. Science 357, 811–815 (2017).

    Google Scholar 

  121. 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).

    ADS  Google Scholar 

  122. Smeets, B. et al. Emergent structures and dynamics of cell colonies by contact inhibition of locomotion. Proc. Natl Acad. Sci. USA 113, 14621–14626 (2016).

    ADS  Google Scholar 

  123. Graner, F. & Glazier, J. A. Simulation of biological cell sorting using a two-dimensional extended Potts model. Phys. Rev. Lett. 69, 2013–2016 (1992).

    ADS  Google Scholar 

  124. Wang, N., Butler, J. P. & Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127 (1993).

    ADS  Google Scholar 

  125. Campas, O. et al. Quantifying cell-generated mechanical forces within living embryonic tissues. Nat. Methods 11, 183–189 (2014).

    Google Scholar 

  126. Colombelli, J. et al. Mechanosensing in actin stress fibers revealed by a close correlation between force and protein localization. J. Cell Sci. 122, 1665 (2009).

    Google Scholar 

  127. Kumar, S. et al. Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization, and extracellular matrix mechanics. Biophys. J. 90, 3762–3773 (2006).

    ADS  Google Scholar 

  128. Thoumine, O. & Ott, A. Time scale dependent viscoelastic and contractile regimes in fibroblasts probed by microplate manipulation. J. Cell Sci. 110, 2109–2116 (1997).

    Google Scholar 

  129. Liang, C. C., Park, A. Y. & Guan, J. L. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat. Protoc. 2, 329–333 (2007).

    Google Scholar 

  130. Gardel, M. L. et al. Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305 (2004).

    ADS  Google Scholar 

  131. Kroy, K. & Glaser, J. The glassy wormlike chain. New J. Phys. 9, 416 (2007).

    ADS  Google Scholar 

  132. Rauzi, M., Verant, P., Lecuit, T. & Lenne, P. F. Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis. Nat. Cell Biol. 10, 1401–1410 (2008).

    Google Scholar 

  133. Blanch-Mercader, C. et al. Effective viscosity and dynamics of spreading epithelia: a solvable model. Soft Matter 13, 1235–1243 (2017).

    ADS  Google Scholar 

  134. Sochacki, K. A. & Taraska, J. W. Correlative fluorescence super-resolution localization microscopy and platinum replica EM on unroofed cells. Methods Mol. Biol. 1663, 219–230 (2017).

    Google Scholar 

  135. O’Rourke, K. P., Dow, L. E. & Lowe, S. W. Immunofluorescent staining of mouse intestinal stem cells. Bio. Protoc. 6 (2016).

  136. Blanch-Mercader, C. & Casademunt, J. Hydrodynamic instabilities, waves and turbulence in spreading epithelia. Soft Matter 13, 6913–6928 (2017).

    ADS  Google Scholar 

  137. Szabo, B. et al. Phase transition in the collective migration of tissue cells: experiment and model. Phys. Rev. E 74, 061908 (2006).

    ADS  Google Scholar 

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Acknowledgements

We apologize to the many colleagues whose work could not be cited owing to space constraints. We thank E. Latorre, F. Giavazzi, R. Cerbino, G. Jacquemet, J. Ivaska, J. Taraska and K. Sochacki for contributing original materials, and all members of our laboratories for critical comments and encouragement. The authors acknowledge support by the Spanish Ministry of Economy, Industry and Competitiveness through the Centro de Excelencia Severo Ochoa Award to the Institute of Bioengineering of Catalonia (X.T.) and through grant BFU2015-65074-P (X.T.), the Generalitat de Catalunya (Cerca Program and 2014-SGR-927 to X.T.), the European Research Council (CoG-616480 to X.T.) and the European Commission (project 731957 to X.T.). E.S. is funded by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001144), the UK Medical Research Council (FC001144) and the Wellcome Trust (FC001144).

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Authors and Affiliations

  1. Institute for Bioengineering of Catalonia, Barcelona, Spain

    Xavier Trepat

  2. Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain

    Xavier Trepat

  3. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

    Xavier Trepat

  4. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain

    Xavier Trepat

  5. The Francis Crick Institute, London, UK

    Erik Sahai

Authors
  1. Xavier Trepat
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  2. Erik Sahai
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Correspondence to Xavier Trepat or Erik Sahai.

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Trepat, X., Sahai, E. Mesoscale physical principles of collective cell organization. Nature Phys 14, 671–682 (2018). https://doi.org/10.1038/s41567-018-0194-9

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