3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration

Daniel Newman, Lorna E. Young, Thomas Waring, Louise Brown, Katarzyna I. Wolanska, Ewan MacDonald, Arthur Charles-Orszag, Benjamin T. Goult, Patrick T. Caswell, Tetsushi Sakuma, Takashi Yamamoto, Laura M. Machesky, Mark R. Morgan, Tobias Zech

Research output: Contribution to journalArticlepeer-review

Abstract

Cell invasion is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through complex 3D extracellular environments. We determine the composition of cell-matrix adhesion complexes of invasive breast cancer cells in 3D matrices and identify an interaction complex required for invasive migration. βPix and myosin18A (Myo18A) drive polarized recruitment of non-muscle myosin 2A (NM2A) to adhesion complexes at the tips of protrusions. Actomyosin force engagement then displaces the Git1-βPix complex from paxillin, establishing a feedback loop for adhesion maturation. We observe active force transmission to the nucleus during invasive migration that is needed to pull the nucleus forward. The recruitment of NM2A to adhesions creates a non-muscle myosin isoform gradient, which extends from the protrusion to the nucleus. We postulate that this gradient facilitates coupling of cell-matrix interactions at the protrusive cell front with nuclear movement, enabling effective invasive migration and front-rear cell polarity.

Original languageEnglish
Article number113554
JournalCell Reports
Volume42
Issue number12
Early online date14 Dec 2023
DOIs
Publication statusPublished - 26 Dec 2023

Keywords

  • actin
  • adhesion
  • contractility
  • CP: Cell biology
  • integrin-based adhesion complexes
  • invasion
  • myosin
  • nuclear force coupling
  • polarity
  • protrusion

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