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Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration

Themistoklis Zisis, View ORCID ProfileDavid B. Brückner, Tom Brandstätter, Joseph d’Alessandro, Angelika M. Vollmar, Chase P. Broedersz, Stefan Zahler
doi: https://doi.org/10.1101/2021.05.07.442718
Themistoklis Zisis
1Ludwig-Maximilians-University Munich, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany
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David B. Brückner
2Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig-Maximilians-University Munich
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  • ORCID record for David B. Brückner
Tom Brandstätter
2Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig-Maximilians-University Munich
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Joseph d’Alessandro
3Institut Jacques Monod (IJM), CNRS UMR 7592 and Université de Paris, 75013, Paris, France
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Angelika M. Vollmar
1Ludwig-Maximilians-University Munich, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany
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Chase P. Broedersz
2Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig-Maximilians-University Munich
4Department of Physics and Astronomy, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
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  • For correspondence: stefan.zahler@cup.uni-muenchen.de c.p.broedersz@vu.nl
Stefan Zahler
1Ludwig-Maximilians-University Munich, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany
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  • For correspondence: stefan.zahler@cup.uni-muenchen.de c.p.broedersz@vu.nl
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Abstract

Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-Cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). Inhibition of E- and N-Cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Lead contact: Stefan Zahler

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 May 08, 2021.
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Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration
Themistoklis Zisis, David B. Brückner, Tom Brandstätter, Joseph d’Alessandro, Angelika M. Vollmar, Chase P. Broedersz, Stefan Zahler
bioRxiv 2021.05.07.442718; doi: https://doi.org/10.1101/2021.05.07.442718
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Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration
Themistoklis Zisis, David B. Brückner, Tom Brandstätter, Joseph d’Alessandro, Angelika M. Vollmar, Chase P. Broedersz, Stefan Zahler
bioRxiv 2021.05.07.442718; doi: https://doi.org/10.1101/2021.05.07.442718

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