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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Leone Rossetti - , Institute for Bioengineering of Catalonia (IBEC) (Autor:in)
  • Steffen Grosser - , Institute for Bioengineering of Catalonia (IBEC) (Autor:in)
  • Juan Francisco Abenza - , Institute for Bioengineering of Catalonia (IBEC), CIBER - Centro de Investigación Biomédica en Red (Autor:in)
  • Léo Valon - , Centre national de la recherche scientifique (CNRS) (Autor:in)
  • Pere Roca-Cusachs - , Institute for Bioengineering of Catalonia (IBEC), Universitat de Barcelona (Autor:in)
  • Ricard Alert - , Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD), Technische Universität Dresden, Exzellenzcluster PoL: Physik des Lebens (Autor:in)
  • Xavier Trepat - , Institute for Bioengineering of Catalonia (IBEC), Centre national de la recherche scientifique (CNRS), Universitat de Barcelona, ICREA (Autor:in)

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

OriginalspracheEnglisch
Seiten (von - bis)1659-1669
Seitenumfang11
FachzeitschriftNature physics
Jahrgang20
Ausgabenummer10
PublikationsstatusVeröffentlicht - Okt. 2024
Peer-Review-StatusJa

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