Abstract
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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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.
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Acknowledgements
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.
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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.
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Supplementary information
Supplementary Information
Methods, Supplementary Figs. 1–10, Table 1 and Videos 1–7.
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.
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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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DOI: https://doi.org/10.1038/s41567-019-0618-1
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