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Dynamic force patterns promote collective cell movements during embryonic wound repair


Embryonic wounds heal rapidly, in a process driven by coordinated cell movements. Polarization of actin and the molecular motor non-muscle myosin II in the cells adjacent to the wound results in the formation of a supracellular cable around the wound that drives repair. In Drosophila embryos, the distribution of actin around wounds is heterogeneous, with regions of high and low actin density, and actin heterogeneity is necessary for rapid repair. Here, we demonstrate that actin and myosin display stochastic patterns around embryonic wounds, and that contractile forces around wounds are heterogeneous. Mathematical modelling suggests that actomyosin heterogeneity favours wound closure if myosin is regulated by tension and strain, a hypothesis that we validate experimentally. We show that inhibition of stretch-activated ion channels disrupts myosin dynamics and tissue repair. Together, our results indicate that staggered contractile events, mechanical signals and force-regulated myosin dynamics coordinate cell behaviours to drive efficient wound closure.

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Fig. 1: Actin and myosin display similar, non-uniform distributions during embryonic wound repair.
Fig. 2: Heterogeneous actomyosin patterns result in non-uniform contraction.
Fig. 3: Myosin is randomly distributed at the wound edge.
Fig. 4: Mechanical regulation of myosin dynamics drives rapid wound repair in silico.
Fig. 5: Local tensile strain is sufficient for myosin localization to the cortex.
Fig. 6: SAICs are required for myosin dynamics during wound repair.


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We are grateful to T. Harris for sharing the myosin II antibody, to M. Hunter and J. Yu for technical assistance, and to C. Tong for help with data annotation. We thank A. McGuigan, C. Simmons and R. Winklbauer for useful discussions; and J. Feng, S. Hopyan, M. Hunter, A. Kobb, C. McFaul and J. Yu for comments on the manuscript. Flybase provided important information for this study. T.Z.-C. was supported by an Ontario Trillium Scholarship and a Doctoral Completion Award from the University of Toronto, and is a World Fellow of the Delta Kappa Gamma International Society. This work was supported by grants to R.F.-G. from the Natural Sciences and Engineering Research Council of Canada (418438-13), the Canada Foundation for Innovation (30279), the Ontario Ministry of Economic Development and Innovation (ER14-10-170), the Ted Rogers Centre for Heart Research TBEP Seed Program, and the Canada First Research Excellence Fund-University of Toronto Medicine by Design. R.F.-G. is the Tier II Canada Research Chair in Quantitative Cell Biology and Morphogenesis.

Author information




T.Z.-C. and R.F.-G. developed the initial ideas for this study, analysed the data and prepared the manuscript. T.Z.-C. performed all experiments.

Corresponding author

Correspondence to Rodrigo Fernandez-Gonzalez.

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Supplementary information

Supplementary Materials

Supplementary Figures 1–15, Supplementary Tables 1 and 2, Supplementary Video Legends 1–10, Supplementary References 1–3

Reporting Summary

Supplementary Video 1

Actin and myosin display similar patterns at the wound margin. Epidermal wound in an embryo co-expressing GFP:MoesinABD and myosin:mCherry. A stack was acquired every 30 s for 1 h and 39 min. Time after wounding is shown. Anterior left, dorsal up.

Supplementary Video 2

Mechanical forces at the wound margin are heterogeneous. Laser ablation experiments in embryos expressing E-cadherin:GFP. Cuts were performed in segments of the actomyosin cable with high (left) or low (right) myosin levels (see Fig. 2a,b). Yellow Xs indicate the sites of ablation. A stack was acquired every 3 s for 66 s. Time after ablation is shown. Anterior left, dorsal up.

Supplementary Video 3

Contraction is faster when the actomyosin distribution is heterogeneous. Heterogeneous (left) and homogeneous (right) patches of the wound margin in embryos expressing E-cadherin:mTomato (green) and myosin:GFP (magenta). Yellow arrowheads indicate the tracked segment. A stack was acquired every 10 s for 1 min.

Supplementary Video 4

Heterogeneous myosin distribution and mechanically regulated dynamics favour rapid wound closure in silico. Wound healing simulations with a heterogeneous myosin distribution and no myosin turnover (left), with tension-based myosin stabilization (centre-left), with strain-based myosin recruitment (centre), or with strain and tension-dependent myosin dynamics (centre-right); or with a homogeneous myosin distribution and strain and tension dependent myosin dynamics (right). Colour indicates interfacial tension in nN based on myosin levels (see Fig. 4 for scale). The simulation time step was 2 s for 20 min. Time is with respect to the onset of wound closure. Anterior left, dorsal up.

Supplementary Video 5

Non-uniform wound edge deformation is associated with embryonic wound repair. Strain maps of the wound edge during embryonic repair. Colour indicates the degree and the type of strain (tensile, cold colours; compressive, warm colours). A stack was acquired every 10 s for 20.3 min. Time after wounding is shown. Anterior left, dorsal up.

Supplementary Video 6

Myosin accumulates at a wound edge segment after being stretched. Relative timing between the deformation of wound edge segment and recruitment of myosin in an embryo expressing E-cadherin:mTomato (green) and myosin:GFP (magenta). Yellow arrowheads indicate the segment of interest. A stack was acquired every 10 s for 20.3 min. Time after wounding is shown. Anterior left, dorsal up.

Supplementary Video 7

Segments mechanically isolated from their neighbours fail to recruit myosin. Wound edge segments in embryos expressing E-cadherin:mTomato (green) and myosin:GFP (magenta) far from the site of wound edge ablation (left) or in a mechanically isolated segment (right). Yellow arrowheads indicate the segments in which fluorescence was monitored. Cyan Xs indicate the segments targeted for ablation. A stack was acquired every 30 s for 20.5 min. Time after segment isolation is shown. Anterior left, dorsal up.

Supplementary Video 8

Tensile strain is sufficient to recruit myosin. Cell interfaces in embryos expressing E-cadherin:mTomato (green) and myosin:GFP (magenta) in sham (left) or UV-irradiated 32 embryos (right). Yellow arrowheads indicate the monitored interfaces. Cyan Xs indicate the cells irradiated to induce strain. A stack was acquired every 10 s for 20.3 min. Time after wounding is shown. Anterior left, dorsal up.

Supplementary Video 9

GsMTx4 treatment impairs wound closure. Wounds in embryos expressing myosin:GFP and injected with buffer (left) or 2.5 mM GsMTx4 (right). A stack was acquired every 30 s for 39 min. Time after injection is shown. Anterior left, dorsal up.

Supplementary Video 10

GdCl3 injection prevents wound repair. Wounds in embryos expressing myosin:GFP and injected with water (left) or 20 mM GdCl3 (right). A stack was acquired every 30 s for 39.5 min. Time after injection is shown. Anterior left, dorsal up.

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

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