Skip to main content

Thank you for visiting 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.

  • Article
  • Published:

Tissue fluidity promotes epithelial wound healing


The collective behaviour of cells in epithelial tissues is dependent on their mechanical properties. However, the contribution of tissue mechanics to wound healing in vivo remains poorly understood. Here, we investigate the relationship between tissue mechanics and wound healing in live Drosophila wing imaginal discs and show that by tuning epithelial cell junctional tension, we can systematically alter the rate of wound healing. Coincident with the contraction of an actomyosin purse string, we observe cells flowing past each other at the wound edge by intercalating, reminiscent of molecules in a fluid, resulting in seamless wound closure. Using a cell-based physical model, we predict that a reduction in junctional tension fluidizes the tissue through an increase in intercalation rate and corresponding reduction in bulk viscosity, in the manner of an unjamming transition. The resultant fluidization of the tissue accelerates wound healing. Accordingly, when we experimentally reduce tissue tension in wing discs, the intercalation rate increases and wounds repair in less time.

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

Access options

Buy this article

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

Fig. 1: Wing disc wound closure is punctuated by wound edge intercalation, which can drive wound closure.
Fig. 2: A vertex model of wound healing predicts that intercalation is necessary for wound closure and cell shape maintenance.
Fig. 3: Wound edge intercalation preserves cell shape.
Fig. 4: Reducing tissue contractility enhances fluidity and can speed wound closure.
Fig. 5: Myosin activity controls tissue fluidity and wound closure rate.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

The code that supports the findings of this study are available from the corresponding author upon reasonable request.


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

    Google Scholar 

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

    ADS  Google Scholar 

  3. Nier, V. et al. Tissue fusion over nonadhering surfaces. Proc. Natl Acad. Sci. USA 112, 9546–9551 (2015).

    ADS  Google Scholar 

  4. Arciero, J. C., Mi, Q., Branca, M. F., Hackam, D. J. & Swigon, D. Continuum model of collective cell migration in wound healing and colony expansion. Biophys. J. 100, 535–543 (2011).

    ADS  Google Scholar 

  5. Brugues, A. et al. Forces driving epithelial wound healing. Nat. Phys. 10, 683–690 (2014).

    Google Scholar 

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

    ADS  Google Scholar 

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

    Google Scholar 

  8. Russo, J. M. et al. Distinct temporal-spatial roles for Rho kinase and myosin light chain kinase in epithelial purse-string wound closure. Gastroenterology 128, 987–1001 (2005).

    Google Scholar 

  9. 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).

    Google Scholar 

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

    Google Scholar 

  11. Brock, J., Midwinter, K., Lewis, J. & Martin, P. Healing of incisional wounds in the embryonic chick wing bud: characterization of the actin purse-string and demonstration of a requirement for Rho activation. J. Cell Biol. 135, 1097–1107 (1996).

    Google Scholar 

  12. Davidson, L. A., Ezin, A. M. & Keller, R. Embryonic wound healing by apical contraction and ingression in Xenopus laevis. Cell Motil. Cytoskeleton 53, 163–176 (2002).

    Google Scholar 

  13. Zulueta-Coarasa, T. & Fernandez-Gonzalez, R. Dynamic force patterns promote collective cell movements during embryonic wound repair. Nat. Phys. 14, 750–758 (2018).

    Google Scholar 

  14. Kobb, A. B., Zulueta-Coarasa, T. & Fernandez-Gonzalez, R. Tension regulates myosin dynamics during Drosophila embryonic wound repair. J. Cell Sci. 130, 689–696 (2017).

    Google Scholar 

  15. Bement, W. M., Forscher, P. & Mooseker, M. S. A novel cytoskeletal structure involved in purse string wound closure and cell polarity maintenance. J. Cell Biol. 121, 565–578 (1993).

    Google Scholar 

  16. Martin, P. & Lewis, J. Actin Cables and epidermal movement in embryonic wound-healing. Nature 360, 179–183 (1992).

    ADS  Google Scholar 

  17. Bement, W. M., Mandato, C. A. & Kirsch, M. N. Wound-induced assembly and closure of an actomyosin purse string in Xenopus oocytes. Curr. Biol. 9, 579–587 (1999).

    Google Scholar 

  18. Danjo, Y. & Gipson, I. K. Actin ‘purse string’ filaments are anchored by E-cadherin-mediated adherens junctions at the leading edge of the epithelial wound, providing coordinated cell movement. J. Cell Sci. 111, 3323–3332 (1998).

    Google Scholar 

  19. Heller, D. et al. EpiTools: an open-source image analysis toolkit for quantifying epithelial growth dynamics. Dev. Cell 36, 103–116 (2016).

    Google Scholar 

  20. Galko, M. J. & Krasnow, M. A. Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol. 2, 1114–1126 (2004).

    Google Scholar 

  21. Losick, V. P., Fox, D. T. & Spradling, A. C. Polyploidization and cell fusion contribute to wound healing in the adult Drosophila epithelium. Curr. Biol. 23, 2224–2232 (2013).

    Google Scholar 

  22. Razzell, W., Wood, W. & Martin, P. Recapitulation of morphogenetic cell shape changes enables wound re-epithelialisation. Development 141, 1814–1820 (2014).

    Google Scholar 

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

    Google Scholar 

  24. Fletcher, A. G., Osterfield, M., Baker, R. E. & Shvartsman, S. Y. Vertex models of epithelial morphogenesis. Biophys. J. 106, 2291–2304 (2014).

    ADS  Google Scholar 

  25. Wyczalkowski, M. A., Varner, V. D. & Taber, L. A. Computational and experimental study of the mechanics of embryonic wound healing. J. Mech. Behav. Biomed. 28, 125–146 (2013).

    Google Scholar 

  26. Barton, D. L., Henkes, S., Weijer, C. J. & Sknepnek, R. Active vertex model for cell-resolution description of epithelial tissue mechanics. PLoS Comput. Biol. 13, e1005569 (2017).

    ADS  Google Scholar 

  27. Staddon, M. F. et al. Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing. PLoS Comput. Biol. 14, e1006502 (2018).

    Google Scholar 

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

    Google Scholar 

  29. Shindo, A. et al. Septin-dependent remodeling of cortical microtubule drives cell reshaping during epithelial wound healing. J. Cell Sci. 131, 212647 (2018).

    Google Scholar 

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

    ADS  Google Scholar 

  31. 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).

    Google Scholar 

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

    ADS  Google Scholar 

  33. Bergantinos, C., Corominas, M. & Serras, F. Cell death-induced regeneration in wing imaginal discs requires JNK signalling. Development 137, 1169–1179 (2010).

    Google Scholar 

  34. Vereshchagina, N. et al. The essential role of PP1 beta in Drosophila is to regulate nonmuscle myosin. Mol. Biol. Cell 15, 4395–4405 (2004).

    Google Scholar 

  35. Amano, M. et al. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J. Biol. Chem. 271, 20246–20249 (1996).

    Google Scholar 

  36. Mizuno, T., Amano, M., Kaibuchi, K. & Nishida, Y. Identification and characterization of Drosophila homolog of Rho-kinase. Gene 238, 437–444 (1999).

    Google Scholar 

  37. 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).

    Google Scholar 

  38. Verboon, J. M. & Parkhurst, S. M. Rho family GTPase functions in Drosophila epithelial wound repair. Small GTPases 6, 28–35 (2015).

    Google Scholar 

  39. Farhadifar, R., Roper, J. C., Algouy, 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 

  40. Chepizhko, O. et al. From jamming to collective cell migration through a boundary induced transition. Soft Matter 14, 3774–3782 (2018).

    ADS  Google Scholar 

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

    Google Scholar 

  42. Fenteany, G., Janmey, P. A. & Stossel, T. P. Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets. Curr. Biol. 10, 831–838 (2000).

    Google Scholar 

  43. 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).

    Google Scholar 

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

    Google Scholar 

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

    ADS  Google Scholar 

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

    ADS  Google Scholar 

  47. Miroshnikova, Y. A. et al. Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification. Nat. Cell Biol. 20, 69–80 (2018).

    Google Scholar 

  48. Firmino, J., Rocancourt, D., Saadaoui, M., Moreau, C. & Gros, J. Cell division drives epithelial cell rearrangements during gastrulation in chick. Dev. Cell 36, 249–261 (2016).

    Google Scholar 

  49. 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).

    Google Scholar 

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

    ADS  Google Scholar 

Download references


R.J.T. was funded by a Medical Research Council Skills Development Fellowship (MR/N014529/1). M.F.S. is supported by an EPSRC funded PhD Studentship at the UCL Department of Physics and Astronomy. D.H. was supported by the Swiss National Science Foundation (31003A-160095). S.B. acknowledges support from Royal Society University Research Fellowship (URF/R1/180187), and a Strategic Fellowship from the UCL Institute for the Physics of Living Systems. Y.M. is funded by a Medical Research Council Fellowship (MR/L009056/1), a UCL Excellence Fellowship, a NSFC International Young Scientist Fellowship (31650110472) and a Lister Institute Research Prize Fellowship. This work was also supported by MRC funding to the MRC LMCB University Unit at UCL (award code MC_U12266B). We thank all members of the Mao group, M. Raff, D. Ish-Horowicz and M. Murrell for providing feedback on the manuscript. We also thank the Baum and Tapon laboratories for sharing fly stocks.

Author information

Authors and Affiliations



R.J.T. and Y.M. conceived the experiments. S.B. and M.F.S. conceived the theory. R.J.T. performed the experiments and analysed the data. M.F.S. ran simulations and analysed the data. D.H. and A.H. developed new image analysis tools in EpiTools and wrote the corresponding methods. R.J.T., M.F.S., S.B. and Y.M. wrote the manuscript.

Corresponding author

Correspondence to Yanlan Mao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information: Nature Physics thanks Marino Arroyo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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

Supplementary information

Supplementary Information

Methods, Supplementary Figs. 1–10, Table 1 and Videos 1–7.

Reporting Summary

Supplementary Video 1

Myosin II localization during Drosophila wing-disc wound closure.

Supplementary Video 2

Wild-type wound closure.

Supplementary Video 3

Vertex-model simulation of wound healing with intercalations disabled.

Supplementary Video 4

Vertex-model simulation of wound healing with intercalations enabled.

Supplementary Video 5

Analysing the first three rows of cells away from the wound.

Supplementary Video 6

Wound closure in an Mbs RNAi wing disc.

Supplementary Video 7

Wound closure in a Rok RNAi wing disc.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tetley, R.J., Staddon, M.F., Heller, D. et al. Tissue fluidity promotes epithelial wound healing. Nat. Phys. 15, 1195–1203 (2019).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


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