Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Adherens junctions as molecular regulators of emergent tissue mechanics

Nature Reviews Molecular Cell Biology volume 25, pages 252–269 (2024)Cite this article

Subjects

Abstract

Tissue and organ development during embryogenesis relies on the collective and coordinated action of many cells. Recent studies have revealed that tissue material properties, including transitions between fluid and solid tissue states, are controlled in space and time to shape embryonic structures and regulate cell behaviours. Although the collective cellular flows that sculpt tissues are guided by tissue-level physical changes, these ultimately emerge from cellular-level and subcellular-level molecular mechanisms. Adherens junctions are key subcellular structures, built from clusters of classical cadherin receptors. They mediate physical interactions between cells and connect biochemical signalling to the physical characteristics of cell contacts, hence playing a fundamental role in tissue morphogenesis. In this Review, we take advantage of the results of recent, quantitative measurements of tissue mechanics to relate the molecular and cellular characteristics of adherens junctions, including adhesion strength, tension and dynamics, to the emergent physical state of embryonic tissues. We focus on systems in which cell–cell interactions are the primary contributor to morphogenesis, without significant contribution from cell–matrix interactions. We suggest that emergent tissue mechanics is an important direction for future research, bridging cell biology, developmental biology and mechanobiology to provide a holistic understanding of morphogenesis in health and disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Adherens junctions are specialized membrane domains.
Fig. 2: Mechanisms for regulation of adherens junctions to modulate mechanics of cell–cell interactions.
Fig. 3: Examples of spatiotemporal variations in 3D tissue mechanics and their molecular control by adherens junctions.
Fig. 4: Mechanics of two-dimensional monolayered epithelia.

Similar content being viewed by others

References

  1. Tepass, U., Troung, K., Godt, D., Ikura, M. & Peifer, M. Cadherins in embyronic and neural morphogenesis. Nat. Rev. Mol. Cell Biol. 1, 91–100 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Mongera, A. et al. A fluid-to-solid jamming transition underlies vertebrate body axis elongation. Nature 561, 401–405 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lenne, P. F. & Trivedi, V. Sculpting tissues by phase transitions. Nat. Commun. 13, 664 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jain, A. et al. Regionalized tissue fluidization is required for epithelial gap closure during insect gastrulation. Nat. Commun. 11, 5604 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tetley, R. J. et al. Tissue fluidity promotes epithelial wound healing. Nat. Phys. 15, 1195–1203 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Petridou, N. I., Grigolon, S., Salbreux, G., Hannezo, E. & Heisenberg, C. P. Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling. Nat. Cell Biol. 21, 169–178 (2019).

    Article  CAS  PubMed  Google Scholar 

  7. Wang, X. et al. Anisotropy links cell shapes to tissue flow during convergent extension. Proc. Natl Acad. Sci. USA 117, 13541–13551 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Atia, L. et al. Geometric constraints during epithelial jamming. Nat. Phys. 14, 629–629 (2018).

    Google Scholar 

  9. Founounou, N. et al. Tissue fluidity mediated by adherens junction dynamics promotes planar cell polarity-driven ommatidial rotation. Nat. Commun. 12, 6974 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Palamidessi, A. et al. Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma. Nat. Mater. 18, 1252–1263 (2019).

    Article  CAS  PubMed  Google Scholar 

  11. Frittoli, E. et al. Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer. Nat. Mater. 22, 644–655 (2023).

    Article  CAS  PubMed  Google Scholar 

  12. Kang, W. et al. A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation. iScience 24, 103252 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Grosser, S. et al. Cell and nucleus shape as an indicator of tissue fluidity in carcinoma. Phys. Rev. X 11, 011033 (2021).

    CAS  Google Scholar 

  14. Campas, O. A toolbox to explore the mechanics of living embryonic tissues. Semin. Cell Dev. Biol. 55, 119–130 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gomez-Gonzalez, M., Latorre, E., Arroyo, M. & Trepat, X. Measuring mechanical stress in living tissues. Nat. Rev. Phys. 2, 300–317 (2020).

    Article  Google Scholar 

  16. Sugimura, K., Lenne, P. F. & Graner, F. Measuring forces and stresses in situ in living tissues. Development 143, 186–196 (2016).

    Article  CAS  PubMed  Google Scholar 

  17. Acharya, B. R. et al. A mechanosensitive RhoA pathway that protects epithelia against acute tensile stress. Dev. Cell 47, 439–452.e6 (2018).

    Article  CAS  PubMed  Google Scholar 

  18. Prakash, V., Bull, M. S. & Prakash, M. Motility-induced fracture reveals a ductile-to-brittle crossover in a simple animal’s epithelia. Nat. Phys. 17, 504–511 (2021).

    Article  CAS  Google Scholar 

  19. Sherwood, D. R. Basement membrane remodeling guides cell migration and cell morphogenesis during development. Curr. Opin. Cell Biol. 72, 19–27 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Walma, D. A. C. & Yamada, K. M. The extracellular matrix in development. Development 147, dev175596 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wu, D., Yamada, K. M. & Wang, S. Tissue morphogenesis through dynamic cell and matrix interactions. Annu. Rev. Cell Dev. Biol. 39, 123–144 (2023).

    Article  CAS  PubMed  Google Scholar 

  22. Bonnans, C., Chou, J. & Werb, Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 15, 786–801 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nelson, C. M. & Bissell, M. J. Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu. Rev. Cell Dev. Biol. 22, 287–309 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rozario, T. & DeSimone, D. W. The extracellular matrix in development and morphogenesis: a dynamic view. Dev. Biol. 341, 126–140 (2010).

    Article  CAS  PubMed  Google Scholar 

  25. Farquhar, M. G. & Palade, G. E. Junctional complexes in various epithelia. J. Cell Biol. 17, 375–412 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Boller, K., Vestweber, D. & Kemler, R. Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J. Cell Biol. 100, 327–332 (1985).

    Article  CAS  PubMed  Google Scholar 

  27. 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 

  28. Tepass, U. & Hartenstein, V. The development of cellular junctions in the Drosophila embryo. Dev. Biol. 161, 563–596 (1994).

    Article  CAS  PubMed  Google Scholar 

  29. Huebner, R. J. et al. Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation. eLife 10, e65390 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mege, 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  Google Scholar 

  31. Ozawa, M. & Kemler, R. Molecular organization of the uvomorulin-catenin complex. J. Cell Biol. 116, 989–996 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Priest, A. V., Shafraz, O. & Sivasankar, S. Biophysical basis of cadherin mediated cell-cell adhesion. Exp. Cell Res. 358, 10–13 (2017).

    Article  CAS  PubMed  Google Scholar 

  33. Rubsam, M. et al. Adherens junctions and desmosomes coordinate mechanics and signaling to orchestrate tissue morphogenesis and function: an evolutionary perspective. Cold Spring Harb. Perspect. Biol. 10, a029207 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Noordstra, I., Morris, R. G. & Yap, A. S. Cadherins and the cortex: a matter of time? Curr. Opin. Cell Biol. 80, 102154 (2023).

    Article  CAS  PubMed  Google Scholar 

  35. Charras, G. & Yap, A. S. Tensile forces and mechanotransduction at cell-cell junctions. Curr. Biol. 28, R445–R457 (2018).

    Article  CAS  PubMed  Google Scholar 

  36. Lecuit, T. & Lenne, P. F. Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nat. Rev. Mol. Cell Biol. 8, 633–644 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Ratheesh, A. et al. Centralspindlin and alpha-catenin regulate Rho signalling at the epithelial zonula adherens. Nat. Cell Biol. 14, 818–828 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Noren, N. K., Liu, B. P., Burridge, K. & Kreft, B. p120 catenin regulates the actin cytoskeleton via rho family GTPases. J. Cell Biol. 150, 567–579 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Noren, N. K., Niessen, C. M., Gumbiner, B. M. & Burridge, K. Cadherin engagement regulates Rho family GTPases. J. Biol. Chem. 276, 33305–33308 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Leckband, D. E. & de Rooij, J. Cadherin adhesion and mechanotransduction. Annu. Rev. Cell Dev. Biol. 30, 291–315 (2014).

    Article  CAS  PubMed  Google Scholar 

  41. Yap, A. S., Duszyc, K. & Viasnoff, V. Mechanosensing and mechanotransduction at cell-cell junctions. Cold Spring Harb. Perspect. Biol. 10, a028761 (2017).

    Article  Google Scholar 

  42. Manibog, K., Li, H., Rakshit, S. & Sivasankar, S. Resolving the molecular mechanism of cadherin catch bond formation. Nat. Commun. 5, 3941 (2014).

    Article  CAS  PubMed  Google Scholar 

  43. Rakshit, S., Zhang, Y., Manibog, K., Shafraz, O. & Sivasankar, S. Ideal, catch, and slip bonds in cadherin adhesion. Proc. Natl Acad. Sci. USA 109, 18815–18820 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Buckley, C. D. et al. The minimal cadherin-catenin complex binds to actin filaments under force. Science 346, 1254211 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ishiyama, N. et al. Force-dependent allostery of the alpha-catenin actin-binding domain controls adherens junction dynamics and functions. Nat. Commun. 9, 5121 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Huang, D. L., Bax, N. A., Buckley, C. D., Weis, W. I. & Dunn, A. R. Vinculin forms a directionally asymmetric catch bond with F-actin. Science 357, 703–706 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Rauskolb, C., Sun, S., Sun, G., Pan, Y. & Irvine, K. D. Cytoskeletal tension inhibits Hippo signaling through an Ajuba-Warts complex. Cell 158, 143–156 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Maitre, J. L. & Heisenberg, C. P. The role of adhesion energy in controlling cell-cell contacts. Curr. Opin. Cell Biol. 23, 508–514 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lenne, P. F., Rupprecht, J. F. & Viasnoff, V. Cell junction mechanics beyond the bounds of adhesion and tension. Dev. Cell 56, 202–212 (2021).

    Article  CAS  PubMed  Google Scholar 

  50. Harrison, O. J. et al. Two-step adhesive binding by classical cadherins. Nat. Struct. Mol. Biol. 17, 348–357 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Pinheiro, D. & Bellaiche, Y. Mechanical force-driven adherens junction remodeling and epithelial dynamics. Dev. Cell 47, 3–19 (2018).

    Article  CAS  PubMed  Google Scholar 

  52. Yap, A. S., Brieher, W. M., Pruschy, M. & Gumbiner, B. M. Lateral clustering of the adhesive ectodomain: a fundamental determinant of cadherin function. Curr. Biol. 7, 308–315 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Angres, B., Barth, A. & Nelson, W. J. Mechanism for transition from initial to stable cell-cell adhesion: kinetic analysis of E-cadherin-mediated adhesion using a quantitative adhesion assay. J. Cell Biol. 134, 549–557 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Ward, M. D., Dembo, M. & Hammer, D. A. Kinetics of cell detachment: peeling of discrete receptor clusters. Biophys. J. 67, 2522–2534 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Mulla, Y. et al. Weak catch bonds make strong networks. Nat. Mater. 21, 1019–1023 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  57. David, R. et al. Tissue cohesion and the mechanics of cell rearrangement. Development 141, 3672–3682 (2014).

    Article  CAS  PubMed  Google Scholar 

  58. 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).

    Article  CAS  PubMed  Google Scholar 

  59. Clement, R., Dehapiot, B., Collinet, C., Lecuit, T. & Lenne, P. F. Viscoelastic dissipation stabilizes cell shape changes during tissue morphogenesis. Curr. Biol. 27, 3132–3142.e4 (2017).

    Article  CAS  PubMed  Google Scholar 

  60. Iyer, K. V., Piscitello-Gomez, R., Paijmans, J., Julicher, F. & Eaton, S. Epithelial viscoelasticity is regulated by mechanosensitive E-cadherin turnover. Curr. Biol. 29, 578–591.e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  61. 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 

  62. Lagendijk, A. K. et al. Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish. Nat. Commun. 8, 1402 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  63. 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 

  64. 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 

  65. Salbreux, G., Charras, G. & Paluch, E. Actin cortex mechanics and cellular morphogenesis. Trends Cell Biol. 22, 536–545 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Roh-Johnson, M. et al. Triggering a cell shape change by exploiting preexisting actomyosin contractions. Science 335, 1232–1235 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Martin, A. C., Kaschube, M. & Wieschaus, E. F. Pulsed contractions of an actin-myosin network drive apical constriction. Nature 457, 495–499 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. 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 

  69. Rauzi, M., Lenne, P. F. & Lecuit, T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature 468, 1110–1114 (2010).

    Article  CAS  PubMed  Google Scholar 

  70. Curran, S. et al. Myosin II controls junction fluctuations to guide epithelial tissue ordering. Dev. Cell 43, 480–492.e6 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Fernandez-Gonzalez, R., Simoes Sde, M., Roper, J. C., Eaton, S. & Zallen, J. A. Myosin II dynamics are regulated by tension in intercalating cells. Dev. Cell 17, 736–743 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Michaux, J. B., Robin, F. B., McFadden, W. M. & Munro, E. M. Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo. J. Cell Biol. 217, 4230–4252 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Priya, R. et al. Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions. Nat. Cell Biol. 17, 1282–1293 (2015).

    Article  CAS  PubMed  Google Scholar 

  74. Munjal, A., Philippe, J. M., Munro, E. & Lecuit, T. A self-organized biomechanical network drives shape changes during tissue morphogenesis. Nature 524, 351–355 (2015).

    Article  CAS  PubMed  Google Scholar 

  75. Brieher, W. M. & Yap, A. S. Cadherin junctions and their cytoskeleton(s). Curr. Opin. Cell Biol. 25, 39–46 (2013).

    Article  CAS  PubMed  Google Scholar 

  76. Reymann, A. C. et al. Actin network architecture can determine myosin motor activity. Science 336, 1310–1314 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Haviv, L., Gillo, D., Backouche, F. & Bernheim-Groswasser, A. A cytoskeletal demolition worker: myosin II acts as an actin depolymerization agent. J. Mol. Biol. 375, 325–330 (2008).

    Article  CAS  PubMed  Google Scholar 

  78. Creton, C. & Ciccotti, M. Fracture and adhesion of soft materials: a review. Rep. Prog. Phys. 79, 046601 (2016).

    Article  PubMed  Google Scholar 

  79. Khalilgharibi, N., Fouchard, J., Recho, P., Charras, G. & Kabla, A. The dynamic mechanical properties of cellularised aggregates. Curr. Opin. Cell Biol. 42, 113–120 (2016).

    Article  CAS  PubMed  Google Scholar 

  80. Serwane, F. et al. In vivo quantification of spatially varying mechanical properties in developing tissues. Nat. Methods 14, 181–186 (2017).

    Article  CAS  PubMed  Google Scholar 

  81. Mongera, A. et al. Mechanics of the cellular microenvironment as probed by cells in vivo during zebrafish presomitic mesoderm differentiation. Nat. Mater. 22, 135–143 (2023).

    Article  CAS  PubMed  Google Scholar 

  82. Le, T. L., Yap, A. S. & Stow, J. L. Recycling of E-cadherin: a potential mechanism for regulating cadherin dynamics. J. Cell Biol. 146, 219–232 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Lock, J. G. & Stow, J. L. Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin. Mol. Biol. Cell 16, 1744–1755 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kozlov, M. M. & Bershadsky, A. D. Processive capping by formin suggests a force-driven mechanism of actin polymerization. J. Cell Biol. 167, 1011–1017 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Carramusa, L., Ballestrem, C., Zilberman, Y. & Bershadsky, A. D. Mammalian diaphanous-related formin dia1 controls the organization of E-cadherin-mediated cell-cell junctions. J. Cell Sci. 120, 3870–3882 (2007).

    Article  CAS  PubMed  Google Scholar 

  86. Forgacs, G., Foty, R. A., Shafrir, Y. & Steinberg, M. S. Viscoelastic properties of living embryonic tissues: a quantitative study. Biophys. J. 74, 2227–2234 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Guevorkian, K., Colbert, M. J., Durth, M., Dufour, S. & Brochard-Wyart, F. Aspiration of biological viscoelastic drops. Phys. Rev. Lett. 104, 218101 (2010).

    Article  PubMed  Google Scholar 

  88. Gonzalez-Rodriguez, D., Guevorkian, K., Douezan, S. & Brochard-Wyart, F. Soft matter models of developing tissues and tumors. Science 338, 910–917 (2012).

    Article  CAS  PubMed  Google Scholar 

  89. Marmottant, P. et al. The role of fluctuations and stress on the effective viscosity of cell aggregates. Proc. Natl Acad. Sci. USA 106, 17271–17275 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhou, J., Kim, H. Y. & Davidson, L. A. Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and neural tube closure. Development 136, 677–688 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhou, J., Kim, H. Y., Wang, J. H. & Davidson, L. A. Macroscopic stiffening of embryonic tissues via microtubules, RhoGEF and the assembly of contractile bundles of actomyosin. Development 137, 2785–2794 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Chu, C. W., Masak, G., Yang, J. & Davidson, L. A. From biomechanics to mechanobiology: Xenopus provides direct access to the physical principles that shape the embryo. Curr. Opin. Genet. Dev. 63, 71–77 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. von Dassow, M. & Davidson, L. A. Natural variation in embryo mechanics: gastrulation in Xenopus laevis is highly robust to variation in tissue stiffness. Dev. Dyn. 238, 2–18 (2009).

    Article  Google Scholar 

  94. Franze, K. Atomic force microscopy and its contribution to understanding the development of the nervous system. Curr. Opin. Genet. Dev. 21, 530–537 (2011).

    Article  CAS  PubMed  Google Scholar 

  95. von Dassow, M., Strother, J. A. & Davidson, L. A. Surprisingly simple mechanical behavior of a complex embryonic tissue. PLoS ONE 5, e15359 (2010).

    Article  Google Scholar 

  96. von Dassow, M., Miller, C. J. & Davidson, L. A. Biomechanics and the thermotolerance of development. PLoS ONE 9, e95670 (2014).

    Article  Google Scholar 

  97. Jackson, T. R., Kim, H. Y., Balakrishnan, U. L., Stuckenholz, C. & Davidson, L. A. Spatiotemporally controlled mechanical cues drive progenitor mesenchymal-to-epithelial transition enabling proper heart formation and function. Curr. Biol. 27, 1326–1335 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Barriga, E. H., Franze, K., Charras, G. & Mayor, R. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo. Nature 554, 523–527 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Marchant, C. L., Malmi-Kakkada, A. N., Espina, J. A. & Barriga, E. H. Cell clusters softening triggers collective cell migration in vivo. Nat. Mater. 21, 1314–1323 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. 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 

  101. Nishizawa, K., Lin, S. Z., Chardes, C., Rupprecht, J. F. & Lenne, P. F. Two-point optical manipulation reveals mechanosensitive remodeling of cell-cell contacts in vivo. Proc. Natl Acad. Sci. USA 120, e2212389120 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Parada, C. et al. Mechanical feedback defines organizing centers to drive digit emergence. Dev. Cell 57, 854–866 e856 (2022).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  104. Mohagheghian, E. et al. Quantifying compressive forces between living cell layers and within tissues using elastic round microgels. Nat. Commun. 9, 1878 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Traber, N. et al. Polyacrylamide bead sensors for in vivo quantification of cell-scale stress in zebrafish development. Sci. Rep. 9, 17031 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. D’Angelo, A., Dierkes, K., Carolis, C., Salbreux, G. & Solon, J. In vivo force application reveals a fast tissue softening and external friction increase during early embryogenesis. Curr. Biol. 29, 1564–1571 e1566 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Lau, K. et al. Anisotropic stress orients remodelling of mammalian limb bud ectoderm. Nat. Cell Biol. 17, 569–579 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kim, S., Pochitaloff, M., Stooke-Vaughan, G. A. & Campas, O. Embryonic tissues as active foams. Nat. Phys. 17, 859–866 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  110. Benazeraf, B. & Pourquie, O. Formation and segmentation of the vertebrate body axis. Annu. Rev. Cell Dev. Biol. 29, 1–26 (2013).

    Article  CAS  PubMed  Google Scholar 

  111. Mongera, A., Michaut, A., Guillot, C., Xiong, F. & Pourquie, O. Mechanics of anteroposterior axis formation in vertebrates. Annu. Rev. Cell Dev. Biol. 35, 259–283 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. McMillen, P. & Holley, S. A. The tissue mechanics of vertebrate body elongation and segmentation. Curr. Opin. Genet. Dev. 32, 106–111 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Benazeraf, B. et al. A random cell motility gradient downstream of FGF controls elongation of an amniote embryo. Nature 466, 248–252 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lawton, A. K. et al. Regulated tissue fluidity steers zebrafish body elongation. Development 140, 573–582 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  116. Sadati, M., Taheri Qazvini, N., 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 

  117. Bonn, D., Denn, M. M., Berthier, L., Divoux, T. & Manneville, S. Yield stress materials in soft condensed matter.Rev. Mod. Phys. 89, 035005 (2017).

    Article  Google Scholar 

  118. Banavar, S. P. et al. Mechanical control of tissue shape and morphogenetic flows during vertebrate body axis elongation. Sci. Rep. 11, 8591 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Cohen-Addad, S., Hohler, R. & Pitois, O. Flow in foams and flowing foams. Annu. Rev. Fluid Mech. 45, 241–267 (2013).

    Article  Google Scholar 

  120. Sumi, A. et al. Adherens junction length during tissue contraction is controlled by the mechanosensitive activity of actomyosin and junctional recycling. Dev. Cell 47, 453–463.e453 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wu, S. K. et al. Cortical F-actin stabilization generates apical-lateral patterns of junctional contractility that integrate cells into epithelia. Nat. Cell Biol. 16, 167–178 (2014).

    Article  CAS  PubMed  Google Scholar 

  122. Khalilgharibi, N. et al. Stress relaxation in epithelial monolayers is controlled by the actomyosin cortex. Nat. Phys. 15, 839 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Cavanaugh, K. E., Staddon, M. F., Munro, E., Banerjee, S. & Gardel, M. L. RhoA mediates epithelial cell shape changes via mechanosensitive endocytosis. Dev. Cell 52, 152–166.e5 (2020).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Morita, H. et al. The physical basis of coordinated tissue spreading in zebrafish gastrulation. Dev. Cell 40, 354–366 e354 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Petridou, N. I., Corominas-Murtra, B., Heisenberg, C. P. & Hannezo, E. Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions. Cell 184, 1914–1928.e19 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Van Hecke, M. Jamming of soft particles: geometry, mechanics, scaling and isostaticity. J. Phys. Condens Mat. 22, 033101 (2010).

    Article  CAS  Google Scholar 

  128. Engl, W., Arasi, B., Yap, L. L., Thiery, J. P. & Viasnoff, V. Actin dynamics modulate mechanosensitive immobilization of E-cadherin at adherens junctions. Nat. Cell Biol. 16, 587–594 (2014).

    Article  CAS  PubMed  Google Scholar 

  129. Smutny, M. et al. Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens. Nat. Cell Biol. 12, 696–702 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Dumortier, J. G. et al. Hydraulic fracturing and active coarsening position the lumen of the mouse blastocyst. Science 365, 465–468 (2019).

    Article  CAS  PubMed  Google Scholar 

  131. Yang, Q. et al. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. Nat. Cell Biol. 23, 733–744 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Schliffka, M. F. & Maitre, J. L. Stay hydrated: basolateral fluids shaping tissues. Curr. Opin. Genet. Dev. 57, 70–77 (2019).

    Article  CAS  PubMed  Google Scholar 

  133. Barua, D., Nagel, M. & Winklbauer, R. Cell-cell contact landscapes in Xenopus gastrula tissues. Proc. Natl Acad. Sci. USA 118, e2017953118 (2021).

    Article  Google Scholar 

  134. Ventura, G. et al. Multiciliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo. Nat. Commun. 13, 6423 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Guignard, L. et al. Contact area-dependent cell communication and the morphological invariance of ascidian embryogenesis. Science 369, eaar5663 (2020).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  137. Heisenberg, C. P. & Bellaiche, Y. Forces in tissue morphogenesis and patterning. Cell 153, 948–962 (2013).

    Article  CAS  PubMed  Google Scholar 

  138. Johnson, J. L., Najor, N. A. & Green, K. J. Desmosomes: regulators of cellular signaling and adhesion in epidermal health and disease. Cold Spring Harb. Perspect. Med. 4, a015297 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Broussard, J. A. et al. The desmoplakin-intermediate filament linkage regulates cell mechanics. Mol. Biol. Cell 28, 3156–3164 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Harris, A. R. et al. Characterizing the mechanics of cultured cell monolayers. Proc. Natl Acad. Sci. USA 109, 16449–16454 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Latorre, E. et al. Active superelasticity in three-dimensional epithelia of controlled shape. Nature 563, 203–208 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Bonfanti, A., Duque, J., Kabla, A. & Charras, G. Fracture in living tissues. Trends Cell Biol. 32, 537–551 (2022).

    Article  PubMed  Google Scholar 

  143. Casares, L. et al. Hydraulic fracture during epithelial stretching. Nat. Mater. 14, 343–351 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Blanchard, G. B. et al. Tissue tectonics: morphogenetic strain rates, cell shape change and intercalation. Nat. Methods 6, 458–464 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Teomy, E., Kessler, D. A. & Levine, H. Confluent and nonconfluent phases in a model of cell tissue. Phys. Rev. E 98, 042418 (2018).

    Article  CAS  Google Scholar 

  146. Higashi, T. & Miller, A. L. Tricellular junctions: how to build junctions at the TRICkiest points of epithelial cells. Mol. Biol. Cell 28, 2023–2034 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Uechi, H. & Kuranaga, E. The tricellular junction protein sidekick regulates vertex dynamics to promote bicellular junction extension. Dev. Cell 50, 327–338.e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  148. Letizia, A. et al. Sidekick is a key component of tricellular adherens junctions that acts to resolve cell rearrangements. Dev. Cell 50, 313–326.e5 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Tang, H. et al. Architecture of cell-cell adhesion mediated by sidekicks. Proc. Natl Acad. Sci. USA 115, 9246–9251 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Cho, Y. et al. Tricellulin secures the epithelial barrier at tricellular junctions by interacting with actomyosin. J. Cell Biol. 221, e202009037 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. 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 

  152. Krndija, D. et al. Active cell migration is critical for steady-state epithelial turnover in the gut. Science 365, 705–710 (2019).

    Article  CAS  PubMed  Google Scholar 

  153. Krajnc, M. Solid-fluid transition and cell sorting in epithelia with junctional tension fluctuations. Soft Matter 16, 3209–3215 (2020).

    Article  CAS  PubMed  Google Scholar 

  154. Levayer, R. & Lecuit, T. Biomechanical regulation of contractility: spatial control and dynamics. Trends Cell Biol. 22, 61–81 (2012).

    Article  PubMed  Google Scholar 

  155. Tetley, R. J. & Mao, Y. The same but different: cell intercalation as a driver of tissue deformation and fluidity. Philos. Trans. R Soc. Lond. 373, 20170328 (2018).

    Article  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Ilina, O. et al. Cell-cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion. Nat. Cell Biol. 22, 1103–1115 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Tachibana, K. et al. Two cell adhesion molecules, nectin and cadherin, interact through their cytoplasmic domain-associated proteins. J. Cell Biol. 150, 1161–1175 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Takahashi, K. et al. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with afadin, a PDZ domain-containing protein. J. Cell Biol. 145, 539–549 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Lin, H. P. et al. Cell adhesion molecule Echinoid associates with unconventional myosin VI/Jaguar motor to regulate cell morphology during dorsal closure in Drosophila. Dev. Biol. 311, 423–433 (2007).

    Article  CAS  PubMed  Google Scholar 

  161. McLachlan, R. W. & Yap, A. S. Not so simple: the complexity of phosphotyrosine signaling at cadherin adhesive contacts. J. Mol. Med. 85, 545–554 (2007).

    Article  CAS  PubMed  Google Scholar 

  162. Braga, V. M. & Yap, A. S. The challenges of abundance: epithelial junctions and small GTPase signalling. Curr. Opin. Cell Biol. 17, 466–474 (2005).

    Article  CAS  PubMed  Google Scholar 

  163. Ireton, R. C. et al. A novel role for p120 catenin in E-cadherin function. J. Cell Biol. 159, 465–476 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Nanes, B. A. et al. p120-catenin binding masks an endocytic signal conserved in classical cadherins. J. Cell Biol. 199, 365–380 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Oakes, P. W. et al. Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres. Nat. Commun. 8, 15817 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Toh, P. J. Y. et al. Optogenetic control of YAP cellular localisation and function. EMBO Rep. 23, e54401 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Ollech, D. et al. An optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells. Nat. Commun. 11, 472 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Izquierdo, E., Quinkler, T. & De Renzis, S. Guided morphogenesis through optogenetic activation of Rho signalling during early Drosophila embryogenesis. Nat. Commun. 9, 2366 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Wu, S. K., Budnar, S., Yap, A. S. & Gomez, G. A. Pulsatile contractility of actomyosin networks organizes the cellular cortex at lateral cadherin junctions. Eur. J. Cell Biol. 93, 396–404 (2014).

    Article  CAS  PubMed  Google Scholar 

  170. Chugh, P. & Paluch, E. K. The actin cortex at a glance. J. Cell Sci. 131, jcs186254 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Bovellan, M. et al. Cellular control of cortical actin nucleation. Curr. Biol. 24, 1628–1635 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Cao, L. et al. SPIN90 associates with mDia1 and the Arp2/3 complex to regulate cortical actin organization. Nat. Cell Biol. 22, 803–814 (2020).

    Article  CAS  PubMed  Google Scholar 

  173. Noordstra, I. et al. An E-cadherin-actin clutch translates the mechanical force of cortical flow for cell-cell contact to inhibit epithelial cell locomotion. Dev. Cell 58, 1748–1763.e6 (2023).

    Article  CAS  PubMed  Google Scholar 

  174. Padmanabhan, A., Ong, H. T. & Zaidel-Bar, R. Non-junctional E-cadherin clusters regulate the actomyosin cortex in the c. elegans zygote. Curr. Biol. 27, 103–112 (2017).

    Article  CAS  PubMed  Google Scholar 

  175. Kovacs, E. M. et al. N-WASP regulates the epithelial junctional actin cytoskeleton through a non-canonical post-nucleation pathway. Nat. Cell Biol. 13, 934–943 (2011).

    Article  CAS  PubMed  Google Scholar 

  176. Tang, V. W. & Brieher, W. α-Actinin-4/FSGS1 is required for Arp2/3-dependent actin assembly at the adherens junction. J. Cell Biol. 196, 115–130 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. 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 

  178. Brasch, J., Harrison, O. J., Honig, B. & Shapiro, L. Thinking outside the cell: how cadherins drive adhesion. Trends Cell Biol. 22, 299–310 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. 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 

  180. 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 

  181. Duong, C. N. et al. Force-induced changes of alpha-catenin conformation stabilize vascular junctions independently of vinculin. J. Cell Sci. 134, jcs259012 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Gowrishankar, K. et al. Active remodeling of cortical actin regulates spatiotemporal organization of cell surface molecules. Cell 149, 1353–1367 (2012).

    Article  CAS  PubMed  Google Scholar 

  183. Chandran, R., Kale, G., Philippe, J. M., Lecuit, T. & Mayor, S. Distinct actin-dependent nanoscale assemblies underlie the dynamic and hierarchical organization of E-cadherin. Curr. Biol. 31, 1726–1736 e1724 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Yap, A. S., Gomez, G. A. & Parton, R. G. Adherens junctions revisualized: organizing cadherins as nanoassemblies. Dev. Cell 35, 12–20 (2015).

    Article  CAS  PubMed  Google Scholar 

  185. Beutel, O., Maraspini, R., Pombo-Garcia, K., Martin-Lemaitre, C. & Honigmann, A. Phase separation of zonula occludens proteins drives formation of tight junctions. Cell 179, 923–936 e911 (2019).

    Article  CAS  PubMed  Google Scholar 

  186. Schwayer, C. et al. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell 179, 937–952.e8 (2019).

    Article  CAS  PubMed  Google Scholar 

  187. Yan, V. T., Narayanan, A., Wiegand, T., Julicher, F. & Grill, S. W. A condensate dynamic instability orchestrates actomyosin cortex activation. Nature 609, 597–604 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Kwak, M. et al. Adherens junctions organize size-selective proteolytic hotspots critical for Notch signalling. Nat. Cell Biol. 24, 1739–1753 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Guo, M. et al. Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy. Cell 158, 822–832 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Bausch, A. R., Moller, W. & Sackmann, E. Measurement of local viscoelasticity and forces in living cells by magnetic tweezers. Biophys. J. 76, 573–579 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Wessel, A. D., Gumalla, M., Grosshans, J. & Schmidt, C. F. The mechanical properties of early Drosophila embryos measured by high-speed video microrheology. Biophys. J. 108, 1899–1907 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Stehbens, S. J. et al. Dynamic microtubules regulate the local concentration of E-cadherin at cell-cell contacts. J. Cell Sci. 119, 1801–1811 (2006).

    Article  CAS  PubMed  Google Scholar 

  193. Bakir, B., Chiarella, A. M., Pitarresi, J. R. & Rustgi, A. K. EMT, MET, plasticity, and tumor metastasis. Trends Cell Biol. 30, 764–776 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Dongre, A. & Weinberg, R. A. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol. 20, 69–84 (2019).

    Article  CAS  PubMed  Google Scholar 

  195. Lamouille, S., Xu, J. & Derynck, R. Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol. 15, 178–196 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. La Porta, C. A. M. & Zapperi, S. Phase transitions in cell migration. Nat. Rev. Phys. 2, 516–517 (2020).

    Article  Google Scholar 

  197. Mitchel, J. A. et al. In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition. Nat. Commun. 11, 5053 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Togashi, H. et al. Nectins establish a checkerboard-like cellular pattern in the auditory epithelium. Science 333, 1144–1147 (2011).

    Article  CAS  PubMed  Google Scholar 

  199. Wei, S. Y. et al. Echinoid is a component of adherens junctions that cooperates with DE-Cadherin to mediate cell adhesion. Dev. Cell 8, 493–504 (2005).

    Article  CAS  PubMed  Google Scholar 

  200. Chang, L. H. et al. Differential adhesion and actomyosin cable collaborate to drive Echinoid-mediated cell sorting. Development 138, 3803–3812 (2011).

    Article  CAS  PubMed  Google Scholar 

  201. Michael, M. & Yap, A. S. The regulation and functional impact of actin assembly at cadherin cell-cell adhesions. Semin. Cell Dev. Biol. 24, 298–307 (2013).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

A.S.Y. and I.N. were supported by grants and fellowships from the National Health and Medical Research Council of Australia (GNT1163462, 2010704) and the Australian Research Council (DP19010287, 190102230) as well as by the European Molecular Biology Organization (EMBO ALTF 251-2018 to I.N.). O.C. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 2068, 390729961) Cluster of Excellence Physics of Life of TU Dresden and by the National Institutes of Health (NIH) in the United States (NIGMS, R01GM135380; NICHD, R01HD095797; NIDCR, R01DE027620).

Author information

Authors and Affiliations

  1. Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany

    Otger Campàs

  2. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

    Otger Campàs

  3. Center for Systems Biology Dresden, Dresden, Germany

    Otger Campàs

  4. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia

    Ivar Noordstra & Alpha S. Yap

Authors
  1. Otger Campàs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivar Noordstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alpha S. Yap
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Otger Campàs or Alpha S. Yap.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Molecular Cell Biology thanks Nicoletta Petridou, Lance Davidson who co-reviewed with Jing Yang, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Advection

Net transport of a substance or particle by the flow of a fluid.

Basal lamina

The extracellular matrix structure that underlies epithelia, containing proteins such as collagen IV and laminin.

Blastoderm

Cell population of the early embryo that will develop into the actual organism.

Catch bonds

Bonds whose lifetime increases on application of tension.

Catch-slip bonds

Bonds whose lifetimes first increase, then decrease, when progressively greater tension is applied.

Cell extrusion

A morphogenetic process, best characterized in epithelia, for which single cells (or small clusters) are physically expelled from tissues in either an apical or basal direction.

Glycocalyx

Specialized glycosoglycan-rich structure found at the apical surfaces of epithelia.

Hippo pathway

A signalling pathway that negatively regulates the Yap/Taz transcriptional co-regulator.

Jamming transition

Phase transition in the rigidity of the tissue, from a fluid to a solid state (or vice versa), that occurs when the volume fraction of cells in the tissue (or spaces between cells) crosses a critical value.

Line tension

Where tension resides in a one-dimensional structure (such as a bicellular junctional belt between cells).

Plastic deformation

Deformation leading to an irreversible change in the structure of a material, causing the material to not return to its original structural state after applied stress is removed.

Rigidity percolation transitions

Transition in the rigidity of a tissue that occurs when the number of bonds between cells in the tissue crosses a critical value.

Simple (Newtonian) fluids

Fluids for which the shear stress depends linearly on the strain rate, with the fluid viscosity being the sole physical parameter characterizing its material properties.

Slip bonds

Bonds whose lifetime decreases with tension.

Trichoplax adhaerens

Marine animal with a flat body plan consisting of two distinct epithelial layers connected at the edges, which moves via ciliary traction on substrates.

Viscoelastic materials

Materials for which their material properties change from elastic (solid) to viscous (fluid), or vice versa, over time.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Campàs, O., Noordstra, I. & Yap, A.S. Adherens junctions as molecular regulators of emergent tissue mechanics. Nat Rev Mol Cell Biol 25, 252–269 (2024). https://doi.org/10.1038/s41580-023-00688-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41580-023-00688-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing