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
- 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
- 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?
- 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.