Investigating the nature of active forces in tissues reveals how contractile cells can form extensile monolayers

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Fulltext

    Accepteret manuskript, 14,5 MB, PDF-dokument

  • Lakshmi Balasubramaniam
  • Doostmohammadi, Amin
  • Thuan Beng Saw
  • Gautham Hari Narayana Sankara Narayana
  • Romain Mueller
  • Tien Dang
  • Minnah Thomas
  • Shafali Gupta
  • Surabhi Sonam
  • Alpha S. Yap
  • Yusuke Toyama
  • Rene-Marc Mege
  • Julia M. Yeomans
  • Benoit Ladoux

Actomyosin machinery endows cells with contractility at a single-cell level. However, within a monolayer, cells can be contractile or extensile based on the direction of pushing or pulling forces exerted by their neighbours or on the substrate. It has been shown that a monolayer of fibroblasts behaves as a contractile system while epithelial or neural progentior monolayers behave as an extensile system. Through a combination of cell culture experiments and in silico modelling, we reveal the mechanism behind this switch in extensile to contractile as the weakening of intercellular contacts. This switch promotes the build-up of tension at the cell-substrate interface through an increase in actin stress fibres and traction forces. This is accompanied by mechanotransductive changes in vinculin and YAP activation. We further show that contractile and extensile differences in cell activity sort cells in mixtures, uncovering a generic mechanism for pattern formation during cell competition, and morphogenesis.

It is now revealed, using cell cultures and in silico models, that weakening intercellular contacts is a fundamental process essential for switching from extensile to contractile tissue behaviour.

OriginalsprogEngelsk
TidsskriftNature Materials
Vol/bind20
Udgave nummer8
Sider (fra-til)1156-1166
Antal sider33
ISSN1476-1122
DOI
StatusUdgivet - 18 feb. 2021

ID: 259106696