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Mechanical stress driven by rigidity sensing governs epithelial stability.

Surabhi Sonam1, Lakshmi Balasubramaniam1, Shao-Zhen Lin2

  • 1Université de Paris, CNRS, Institut Jacques Monod, F-75006 Paris, France.

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|January 23, 2023
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Epithelial cells lose integrity on soft substrates due to mechanical stress. Substrate stiffness influences cell mechanics, leading to hole formation and potential tissue damage.

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Area of Science:

  • Cell biology
  • Biophysics
  • Materials science

Background:

  • Epithelial cells form a critical barrier against environmental stress.
  • The mechanical properties of the cellular environment can impact epithelial integrity.
  • How substrate mechanics influence epithelial monolayer integrity is not well understood.

Purpose of the Study:

  • To investigate the impact of substrate stiffness on epithelial monolayer integrity.
  • To elucidate the mechanical mechanisms underlying epithelial hole formation.
  • To understand the role of mechanical stress and topological defects in epithelial failure.

Main Methods:

  • Culturing epithelial cells on 2D hydrogels of varying stiffness.
  • Observing monolayer integrity and hole formation.
  • Utilizing active nematic modeling to analyze mechanical states.
  • Investigating the role of cell-cell junctions and cellular stretching.

Main Results:

  • Epithelial monolayers lose integrity and form holes on soft substrates.
  • Substrate stiffness induces a switch from tensile to compressive mechanical states.
  • Spontaneous topological defects, specifically half-integer defects, drive hole formation.
  • Weakening of cell-cell junctions promotes monolayer rupture under tensile stress.

Conclusions:

  • Substrate stiffness provides feedback on epithelial monolayer mechanical states.
  • Topological defects can trigger stochastic mechanical failure in epithelial monolayers.
  • Findings offer insights into compromised epithelial integrity during immune responses and morphogenesis.