This study investigated possible mechanisms underlying differences between heterophilic and homophilic cadherin adhesions that influence intercellular mechanics and multicellular organization. Results suggest that homophilic cadherin ligation selectively activates force-transduction, such that resulting signaling and mechano-transduction amplitudes are independent of cadherin binding affinities. Epithelial (E-) and neural (N-) cadherin cooperate with distinct growth factors to mechanically activate force-transduction cascades. Prior results demonstrated that E-cadherin and epidermal growth factor receptor form force-sensitive complexes at intercellular junctions. Here, results show that the reconstitution of N-cadherin force transduction required the co-expression of N-cadherin and fibroblast growth factor receptor. Mechanical measurements further demonstrated that homophilic ligation initiates receptor tyrosine kinase-dependent force transduction cascades, but heterophilic cadherin ligands fail to activate signaling or generate stereotypical mechano-transduction signatures. The all-or-nothing contrast between mechano-transduction by heterophilic versus homophilic cadherin adhesions supersedes differences in cadherin adhesion strength. This mechano-selectivity impacts cell spreading and traction generation on cadherin substrates. Homophilic ligation appears to be a key that selectively unlocks cadherin mechano-transduction. These findings may reconcile the roles of cadherin recognition and cell mechanics in the organization of multicellular assemblies.
Cadherins and Growth Factor Receptors: ligand selective mechano-switches at cadherin junctions
These authors contributed equally to the work
- Award Group:
- Funder(s): National Institutes of Health
- Award Id(s): 1 RO1 GM131425-01
- Funder(s):
- Award Group:
- Funder(s): National Institutes of Health
- Award Id(s): T32-GM136629
- Funder(s):
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Vinh Vu, Brendan Sullivan, Evan Hebner, Zainab Rahil, Yubo Zou, Deborah Leckband; Cadherins and Growth Factor Receptors: ligand selective mechano-switches at cadherin junctions. J Cell Sci 2025; jcs.262279. doi: https://doi.org/10.1242/jcs.262279
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