Actomyosin controls planarity and folding of epithelia in response to compression


Throughout embryonic development and adult life, epithelia are subjected to compressive deformations. While these have been shown to trigger mechanosensitive responses such as cell extrusion and differentiation, which span tens of minutes, little is known about how epithelia adapt to compression over shorter timescales. Here, using suspended epithelia, we uncover the immediate response of epithelial tissues to the application of in-plane compressive strains (5–80%). We show that fast compression induces tissue buckling followed by actomyosin-dependent tissue flattening that erases the buckle within tens of seconds, in both mono- and multi-layered epithelia. Strikingly, we identify a well-defined limit to this response, so that stable folds form in the tissue when compressive strains exceed a ‘buckling threshold’ of ~35%. A combination of experiment and modelling shows that this behaviour is orchestrated by adaptation of the actomyosin cytoskeleton as it re-establishes tissue tension following compression. Thus, tissue pre-tension allows epithelia to both buffer against deformation and sets their ability to form and retain folds during morphogenesis.

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Fig. 1: Fast mechanical adaptation of epithelia to compression.
Fig. 2: Tissue flattening is achieved through myosin-dependent cell shape change.
Fig. 3: Pre-tension buffers against compression to prevent stable buckling of epithelia.
Fig. 4: Epithelia behave as a pre-tensed viscoelastic material.
Fig. 5: Pre-tension and stiffness predict the buckling threshold.

Data availability

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

Code availability

All code created for the analysis of the data in this study is available from the corresponding authors upon reasonable request.


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The authors wish to acknowledge past and present members of the Charras, Baum and Kabla laboratories and Ys for stimulating discussions as well as D. Farquharson and S. Townsend at the UCL workshop. T.P.J.W. and N.K. were part of the EPSRC funded doctoral training programme CoMPLEX. J.F. and P.R. were funded by BBSRC grants (nos. BB/M003280 and BB/M002578) to G.T.C. and A.J.K. N.K. was funded by the Rosetrees Trust and the UCL Graduate School through a UCL Overseas Research Scholarship. A.L. was supported by an EMBO long-term post-doctoral fellowship. B.B. was supported by UCL, a BBSRC project grant (no. BB/K009001/1) and a CRUK programme grant (no. 17343). T.P.J.W., J.F., N.K., A.L. and G.T.C. were supported by a consolidator grant from the European Research Council to G.T.C. (MolCellTissMech, agreement no. 647186).

Author information

T.P.J.W., J.F., B.B. and G.T.C. designed the experiments. T.P.J.W., J.F., A.L. and N.K. carried out the experiments. T.P.J.W. and J.F. performed the data and image analysis. P.R. and A.J.K. designed the rheological model. T.P.J.W., J.F., B.B. and G.T.C. wrote the manuscript. All authors discussed the results and manuscript.

Correspondence to Buzz Baum or Alexandre J. Kabla or Guillaume T. Charras.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–6, Supplementary Notes 1–4, Supplementary refs. 1–4 and Supplementary Video 1–9.

Reporting Summary

Supplementary Video 1

Epithelial response to fast −35% strain application.

Supplementary Video 2

Epithelial response to fast −50% strain application.

Supplementary Video 3

Epithelial response to slow −80% strain application.

Supplementary Video 4

HaCaT response to fast −35% strain application.

Supplementary Video 5

HaCaT response to fast −50% strain application.

Supplementary Video 6

HaCaT response to slow −80% strain application.

Supplementary Video 7

Epithelial flattening requires actomyosin activity.

Supplementary Video 8

Dependence of flattening time on strain history.

Supplementary Video 9

Reversibility of the change in flattening time.

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