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Abstract Mechanical interactions between cells have been shown to play critical roles in regulating cell signaling and communications. However, the precise measurement of intercellular forces is still quite challenging, especially considering the complex environment at cell–cell junctions. In this study, we report a fluorescence lifetime‐based approach to image and quantify intercellular molecular tensions. Using this method, tensile forces among multiple ligand–receptor pairs can be measured simultaneously. We first validated our approach and developed lifetime measurement‐based DNA tension probes to image E‐cadherin‐mediated tension on epithelial cells. These probes were then further applied to quantify the correlations between E‐cadherin and N‐cadherin tensions during an epithelial–mesenchymal transition process. The modular design of these probes can potentially be used to study the mechanical features of various physiological and pathological processes.
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This content will become publicly available on February 1, 2026
Cadherins and growth factor receptors – ligand-selective mechano-switches at cadherin junctions
ABSTRACT 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 have demonstrated that E-cadherin and epidermal growth factor receptor form force-sensitive complexes at intercellular junctions. Here, we show that the reconstitution of N-cadherin force transduction requires 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 might reconcile the roles of cadherin recognition and cell mechanics in the organization of multicellular assemblies.
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- PAR ID:
- 10616268
- Editor(s):
- Green, Kathleen
- Publisher / Repository:
- The Company of Biologists
- Date Published:
- Journal Name:
- Journal of Cell Science
- Volume:
- 138
- Issue:
- 3
- ISSN:
- 0021-9533
- Subject(s) / Keyword(s):
- cadherin mechanoselectivity growth factor receptor adhesion
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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