E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch

Borghi, Nicolas, et al. “E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch.” Proceedings of the National Academy of Sciences 109.31 (2012): 12568-12573.

Summary & Highlights

  • Cadherins: intercellular adhesion complexes
    • Extracellular: form bonds with cadherins on neighboring cells
    • Intracellular: recruits catenin, associate with additional cytoskeleton binding and regulatory proteins// binds beta-catenin, then alpha-catenin
  • Used FRET to test the origin & magnitude of tensile forces transmitted through cytoplasmic domain of E-cadherin in epithelial cells
    • Actomyosin cytoskeleton exerts pN-tensile force on E-cadherin, which requires the catenin-binding domain
  • High FRET = low tension // low FRET = high tension
  • In vitro, cadherin/catenin forms weak bond with actin
  • Made variant E-cadherin (EcadTSMod) that contained a tension sensor module (TSMod) inserted in the cytoplasmic domain between transmembrane domain and the catenin binding domain
  • Actin filaments and myosin II activity require alpha-catenin to exert constitutive tension on the cytoplasmic domain of E-cadherin
  • Results
    • E-cahderin cytoplasmic domain is under tension that is dependent on an intact actin cytoskeleton, aE-catenin and myosin II activity
    • Tension generated by the actomyosin cytoskeleton on E-cadherin is constitutive, regardless whether E-cadherin localized within or outside of cell-cell contacts at plasma membrane
    • Tension in the cytoplasmic domain of E-cadherin is increased specifically at cell-cell contacts upon externally applied uniaxial stretch

Future Questions

  • Signaling pathways downstream of mechanically stimulated cadherins
  • How does this apply in 3D?
  • How do surface properties affect the measured tension levels in the cell?

Personal Thoughts

  • Cytochalasin B, inhibitor of actin polymerization
  • ML7, inhibitor of myosin light chain kinase
  • In this study, only looked at the border between two cells… would results change if cells were on all sides?
  • Is it even possible to do this in 3D?
  • During collective migration, how is this affected?
  • Didn’t test how different surface stiffnesses affect the forces measured within this cell.
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