Optogenetic generation of leader cells reveals a force–velocity relation for collective cell migration

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Leone Rossetti - , Institute for Bioengineering of Catalonia (IBEC) (Author)
  • Steffen Grosser - , Institute for Bioengineering of Catalonia (IBEC) (Author)
  • Juan Francisco Abenza - , Institute for Bioengineering of Catalonia (IBEC), CIBER - Bioengineering, Biomaterials and Nanomedicine (Author)
  • Léo Valon - , French National Centre for Scientific Research (CNRS) (Author)
  • Pere Roca-Cusachs - , Institute for Bioengineering of Catalonia (IBEC), University of Barcelona (Author)
  • Ricard Alert - , Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), TUD Dresden University of Technology, Clusters of Excellence PoL: Physics of Life (Author)
  • Xavier Trepat - , Institute for Bioengineering of Catalonia (IBEC), French National Centre for Scientific Research (CNRS), University of Barcelona, ICREA - Catalan Institution for Research and Advanced Studies (Author)

Abstract

During development, wound healing and cancer invasion, migrating cell clusters feature highly protrusive leader cells at their front. Leader cells are thought to pull and direct their cohort of followers, but whether their local action is enough to guide the entire cluster, or if a global mechanical organization is needed, remains controversial. Here we show that the effectiveness of the leader–follower organization is proportional to the asymmetry of traction and tension within cell clusters. By combining hydrogel micropatterning and optogenetic activation, we generate highly protrusive leaders at the edge of minimal cell clusters. We find that the induced leader can robustly drag one follower but not larger groups. By measuring traction forces and tension propagation in clusters of increasing size, we establish a quantitative relationship between group velocity and the asymmetry of the traction and tension profiles. Modelling motile clusters as active polar fluids, we explain this force–velocity relationship in terms of asymmetries in the active traction profile. Our results challenge the notion of autonomous leader cells, showing that collective cell migration requires global mechanical organization within the cluster.

Details

Original languageEnglish
Pages (from-to)1659-1669
Number of pages11
JournalNature physics
Volume20
Issue number10
Publication statusPublished - Oct 2024
Peer-reviewedYes

Keywords

Sustainable Development Goals

ASJC Scopus subject areas