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.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
The code that supports the findings of this study are available from the corresponding author upon reasonable request.
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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.
The authors declare no competing interests.
Peer review information: Nature Physics thanks Marino Arroyo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Methods, Supplementary Figs. 1–10, Table 1 and Videos 1–7.
Myosin II localization during Drosophila wing-disc wound closure.
Wild-type wound closure.
Vertex-model simulation of wound healing with intercalations disabled.
Vertex-model simulation of wound healing with intercalations enabled.
Analysing the first three rows of cells away from the wound.
Wound closure in an Mbs RNAi wing disc.
Wound closure in a Rok RNAi wing disc.
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Tetley, R.J., Staddon, M.F., Heller, D. et al. Tissue fluidity promotes epithelial wound healing. Nat. Phys. 15, 1195–1203 (2019). https://doi.org/10.1038/s41567-019-0618-1
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