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On the mechanical regulation of epithelial tissue homeostasis

Sara Kaliman, View ORCID ProfileMaxime Hubert, Carina Wollnik, Lovro Nuić, Damir Vurnek, Simone Gehrer, Jakov Lovrić, View ORCID ProfileDiana Dudziak, View ORCID ProfileFlorian Rehfeldt, View ORCID ProfileAna-Sunčana Smith
doi: https://doi.org/10.1101/2021.04.10.439119
Sara Kaliman
1PULS Group, Department of Physics, FAU Erlangen-Nürnberg, IZNF, Erlangen, Germany
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Maxime Hubert
1PULS Group, Department of Physics, FAU Erlangen-Nürnberg, IZNF, Erlangen, Germany
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  • ORCID record for Maxime Hubert
Carina Wollnik
2rd, 37077 Göttingen, Germany
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Lovro Nuić
3Group for Computational Life Sciences, Ruder Boskovic Institute, Zagreb, Croatia
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Damir Vurnek
1PULS Group, Department of Physics, FAU Erlangen-Nürnberg, IZNF, Erlangen, Germany
4Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University of Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany
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Simone Gehrer
1PULS Group, Department of Physics, FAU Erlangen-Nürnberg, IZNF, Erlangen, Germany
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Jakov Lovrić
3Group for Computational Life Sciences, Ruder Boskovic Institute, Zagreb, Croatia
1PULS Group, Department of Physics, FAU Erlangen-Nürnberg, IZNF, Erlangen, Germany
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Diana Dudziak
4Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University of Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany
5Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany
6Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany
7Medical Immunology Campus Erlangen, Erlangen, Germany
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Florian Rehfeldt
2rd, 37077 Göttingen, Germany
8University of Bayreuth, Experimental Physics 1, 95440 Bayreuth, Germany
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  • For correspondence: maxime.hubert@fau.de florian.rehfeldt@unibayreuth.de smith@physik.fau.de
Ana-Sunčana Smith
1PULS Group, Department of Physics, FAU Erlangen-Nürnberg, IZNF, Erlangen, Germany
3Group for Computational Life Sciences, Ruder Boskovic Institute, Zagreb, Croatia
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  • For correspondence: maxime.hubert@fau.de florian.rehfeldt@unibayreuth.de smith@physik.fau.de
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Abstract

Despite recent efforts to understand homeostasis in epithelial tissues, there are many unknowns surrounding this steady state. It is considered to be regulated by mechanoresponse, but unlike for single cells, this remains heavily debated for tissues. Here, we show that changes in matrix stiffness induce a non-equilibrium transition from tubular to squamous Madin-Darby Canine Kidney II tissues. Nonetheless, despite different cell morphologies and densities, all homeostatic tissues display equivalent topologies, which, hence, must be actively targeted and regulated. On the contrary, the mechanoresponse induces dramatic changes in the large-scale organization of the colonies. On stiff gels, this yields an unreported cooperative state of motile cells displaying higher densities than in the arrested homeostatic state. This suggests a more complex relation between cell density and motility than previously anticipated. Our results unequivocally relate the mechanosensitive properties of individual cells to the evolving macroscopic structures, an effect that could be important for understanding the emergent pathologies of living tissues.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted April 11, 2021.
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On the mechanical regulation of epithelial tissue homeostasis
Sara Kaliman, Maxime Hubert, Carina Wollnik, Lovro Nuić, Damir Vurnek, Simone Gehrer, Jakov Lovrić, Diana Dudziak, Florian Rehfeldt, Ana-Sunčana Smith
bioRxiv 2021.04.10.439119; doi: https://doi.org/10.1101/2021.04.10.439119
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On the mechanical regulation of epithelial tissue homeostasis
Sara Kaliman, Maxime Hubert, Carina Wollnik, Lovro Nuić, Damir Vurnek, Simone Gehrer, Jakov Lovrić, Diana Dudziak, Florian Rehfeldt, Ana-Sunčana Smith
bioRxiv 2021.04.10.439119; doi: https://doi.org/10.1101/2021.04.10.439119

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