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Multiscale mechanisms driving tissue rupture by invading cells.

Selwin K Wu1, Fuqiang Sun2, Celestine Z Ho3

  • 1Mechanobiology Institute, National University of Singapore, Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.

Developmental Cell
|March 5, 2026
PubMed
Summary

Tissue barriers actively contribute to collective cell invasion by rupturing, challenging existing models. Invasive cells and barriers coordinate contractility for tissue penetration, independent of jamming.

Keywords:
E-cadherinactive wettingapical constrictioncollective cell invasionintegrin adhesionjamming transitionovarian cancer metastasisphase transitiontensile fracturetissue mechanics

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Area of Science:

  • Cell biology
  • Biophysics
  • Cancer research

Background:

  • Collective cell invasion is crucial in development, immunity, and cancer.
  • Prevailing theories suggest invading cells 'unjam' and push through barriers.
  • The active role of tissue barriers in invasion remains poorly understood.

Purpose of the Study:

  • To investigate the mechanical role of tissue barriers in collective cell invasion.
  • To elucidate the molecular and cellular mechanisms driving invasion across barriers.
  • To challenge current paradigms of collective cell invasion.

Main Methods:

  • Utilized ovarian adenocarcinoma spheroids invading mesothelium as an experimental model.
  • Combined experimental observations with computational modeling.
  • Analyzed invasion across molecular to multicellular scales.

Main Results:

  • Identified intercellular integrin adhesions between invasive leader cells and the tissue barrier.
  • Demonstrated that these adhesions trigger apical constrictions within the barrier.
  • Showed that coordinated subcellular contractility drives barrier rupture and invasion, independent of jamming.

Conclusions:

  • Tissue barriers actively participate in collective cell invasion through mechanical rupture.
  • Invasion is driven by coordinated contractility between invading cells and the barrier, not solely by cell pushing.
  • Findings challenge the established understanding of collective cell invasion mechanisms.