Mechanosensitive Junction Remodeling Promotes Robust Epithelial Morphogenesis

Biophys J. 2019 Nov 5;117(9):1739-1750. doi: 10.1016/j.bpj.2019.09.027. Epub 2019 Sep 28.


Morphogenesis of epithelial tissues requires tight spatiotemporal coordination of cell shape changes. In vivo, many tissue-scale shape changes are driven by pulsatile contractions of intercellular junctions, which are rectified to produce irreversible deformations. The functional role of this pulsatory ratchet and its mechanistic basis remain unknown. Here we combine theory and biophysical experiments to show that mechanosensitive tension remodeling of epithelial cell junctions promotes robust epithelial shape changes via ratcheting. Using optogenetic control of actomyosin contractility, we find that epithelial junctions show elastic behavior under low contractile stress, returning to their original lengths after contraction, but undergo irreversible deformation under higher magnitudes of contractile stress. Existing vertex-based models for the epithelium are unable to capture these results, with cell junctions displaying purely elastic or fluid-like behaviors, depending on the choice of model parameters. To describe the experimental results, we propose a modified vertex model with two essential ingredients for junction mechanics: thresholded tension remodeling and continuous strain relaxation. First, junctions must overcome a critical strain threshold to trigger tension remodeling, resulting in irreversible junction length changes. Second, there is a continuous relaxation of junctional strain that removes mechanical memory from the system. This enables pulsatile contractions to further remodel cell shape via mechanical ratcheting. Taken together, the combination of mechanosensitive tension remodeling and junctional strain relaxation provides a robust mechanism for large-scale morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomechanical Phenomena
  • Caco-2 Cells
  • Computer Simulation
  • Elasticity
  • Epithelial Cells / metabolism
  • Epithelium / growth & development*
  • Humans
  • Intercellular Junctions / metabolism*
  • Mechanotransduction, Cellular*
  • Models, Biological
  • Morphogenesis*
  • Optogenetics
  • Viscosity
  • rho GTP-Binding Proteins / metabolism


  • rho GTP-Binding Proteins