Epithelial monolayers are one-cell-thick tissue sheets that line most of the body surfaces, separating internal and external environments. As part of their function, they must withstand extrinsic mechanical stresses applied at high strain rates. However, little is known about how monolayers respond to mechanical deformations. Here, by subjecting suspended epithelial monolayers to stretch, we find that they dissipate stresses on a minute timescale and that relaxation can be described by a power law with an exponential cut-off at timescales larger than about 10 s. This process involves an increase in monolayer length, pointing to active remodelling of cellular biopolymers at the molecular scale during relaxation. Strikingly, monolayers consisting of tens of thousands of cells relax stress with similar dynamics to single rounded cells, and both respond similarly to perturbations of the actomyosin cytoskeleton. By contrast, cell–cell junctional complexes and intermediate filaments do not relax tissue stress, but form stable connections between cells, allowing monolayers to behave rheologically as single cells. Taken together, our data show that actomyosin dynamics governs the rheological properties of epithelial monolayers, dissipating applied stresses and enabling changes in monolayer length.
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The authors wish to acknowledge present and past members of the Charras, Baum, Kabla and Muñoz laboratories for discussions. The authors acknowledge technical support from UCL Genomics for sequencing and analysing total RNA data as well as from J. Duque (LCN) for analysis of fluorescence intensity at junctions and from M. Vaghela (LCN) for AFM measurements. N.K. was funded by the Rosetrees Trust, the UCL Graduate School, the EPSRC funded doctoral training programme CoMPLEX and the European Research Council (ERC-CoG MolCellTissMech, agreement 647186 to G.C.). N.K. was in receipt of a UCL Overseas Research Scholarship. N.K. was supported by the Professor Rob Seymour Travel Bursary Fund for research visits to Barcelona. J.F. and A.B. were funded by BBSRC grants (BB/M003280 and BB/M002578) to G.C. and A.K. J.J.M., N.A. and P.M. acknowledge the support of the Ministry of Economy, Industry and Competitiveness through grants nos. DPI2013-43727R and DPI2016-74929-R and the Generalitat de Catalunya through grant no. 2014-SGR-1471. N.A. was also financially supported by Universitat Politècnica de Catalunya and Consorci Escola Industrial de Barcelona through grant UPC-FPI 2012, and the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007–2013)/ERC, grant agreement no. 240487. P.M. was also supported by the European Molecular and Biology Organization under grant ASTF 351-2016. R.B. is part of the EPSRC-funded doctoral training programme CoMPLEX. M.D. was funded by a Marie Skłodowska-Curie Horizon 2020 Individual Fellowship (MRTGS). A.Y. was supported by an HFSP Young Investigator award to G.C. (RGY 66/2013). A.H. was supported by a BBSRC grant (BB/K013521) to G.C. and A.K. Y.F. was supported by Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research on Innovative Areas 26114001, Grant-in-Aid for Scientific Research (A) 18H03994, the Strategic Japanese–Swiss Science and Technology Programme, AMED under grant nos. JP17ck0106361 and JP18cm0106234, SAN-ESU GIKEN Co. Ltd, the Naito Foundation and the Takeda Science Foundation. A.K. was supported by BBSRC grants (BB/K018175/1, BB/M003280 and BB/M002578). Y.M. is funded by MRC Fellowship MR/L009056/1, a UCL Excellence Fellowship and NSFC International Young Scientist Fellowship 31650110472. B.B. is supported by UCL, a BBSRC project grant (BB/K009001/1) and a CRUK programme grant (17343). M.M. is supported by EPSRC (EP/K038656/1). G.C. is supported by a consolidator grant from the European Research Council (MolCellTissMech, agreement 647186). Atomic force microscopy equipment was purchased thanks to an ALERT16 grant from BBSRC to G.C.
The authors declare no competing interests.
Journal peer review information: Nature Physics thanks Pierre-François Lenne and the other anonymous reviewer(s) for their contribution to the peer review of this work.
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Supplementary Figs. 1–20, Supplementary Tables 1–5, Supplementary Results, Supplementary Methods and Supplementary References 1–21.
Cross-section view of a monolayer expressing E-cadherin–GFP before, during and after stretch. The monolayer is stretched at 0 s and the strain is maintained constant at 30% until 129.6 s, after which the rod is returned to its initial position. The length of the monolayer on release is different from its length before application of stretch and, as a consequence, it buckles. The monolayer appears in green, the surrounding medium appears in magenta due to inclusion of Alexa-647 and the glass substrates on either side of the suspended monolayer appear dark due to dye exclusion. Scale bar: 100 μm.
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Khalilgharibi, N., Fouchard, J., Asadipour, N. et al. Stress relaxation in epithelial monolayers is controlled by the actomyosin cortex. Nat. Phys. 15, 839–847 (2019). https://doi.org/10.1038/s41567-019-0516-6
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