Mechanotransduction in Epithelial Cell-Cell Adhesion

Mechanotransduction in epithelial cell–cell adhesion describes how physical forces at cell junctions are converted into biochemical signals that regulate tissue integrity, barrier function and morphogenesis. At the heart of this process lie adherens junctions, where transmembrane cadherin receptors form homophilic bonds and link via β-catenin and α-catenin to the actin cytoskeleton. Mechanical tension generated by myosin motors or external stresses pulls on these complexes, triggering force-dependent conformational changes in α-catenin and recruiting scaffolding proteins such as vinculin. This dynamic coupling stabilises junctions under load, modulates junctional remodelling during development and repair, and governs collective cell behaviours. Dysregulation of mechanotransduction pathways underlies a range of pathologies, from impaired epithelial barriers in inflammatory bowel disease to aberrant cell dispersal in carcinoma. Understanding the molecular choreography that translates mechanical cues into adhesion strengthening and cytoskeletal reorganisation offers routes to novel therapeutic strategies and informs the design of biomimetic materials.

Research from Nature Portfolio

Recent studies have elucidated how α-catenin structural states govern force sensing and junctional resilience. High-resolution cryo-EM has captured the initial engagement of both monomeric and dimeric α-catenin with filamentous actin, revealing inter-domain interactions that enable catch-bond formation under tension. This work clarifies how cytoskeletal forces unfold α-catenin to strengthen links between cadherin complexes and actin. Complementing this, investigations into epithelial barrier pathology have shown that aberrant upregulation of an E3 ubiquitin ligase can drive degradation of key actin-regulatory kinases, undermining cortical actin assembly and compromising junction integrity. These insights bridge fundamental mechanotransduction mechanisms with disease contexts, highlighting how force-dependent stabilisation of junctions can be subverted in inflammation.

Mechanotransduction in Epithelial Cell-Cell Adhesion publication trend

The graph below shows the total number of articles in mechanotransduction in epithelial cell-cell adhesion across all publications each year (not limited to Nature Index journals).

Technical terms

Mechanotransduction: Conversion of mechanical stimuli into intracellular biochemical signals.

Adherens junction: Cell–cell adhesion complex primarily formed by cadherins and catenins linked to actin.

α-Catenin: Cytoskeletal adaptor protein that undergoes force-dependent conformational change to bind actin.

E-Cadherin: Transmembrane adhesion receptor mediating homophilic cell–cell binding in epithelia.

F-Actin: Filamentous actin that forms the structural framework of the cytoskeleton.

Vinculin: Actin-binding protein recruited under tension to reinforce cell–cell and cell–matrix adhesions.

References

1. TRIM40 is a pathogenic driver of inflammatory bowel disease subverting intestinal barrier integrity. Nature Communications (2023).
2. Distinct inter-domain interactions of dimeric versus monomeric α-catenin link cell junctions to filaments. Communications Biology (2023).
3. α-Catenin and Vinculin Cooperate to Promote High E-cadherin-based Adhesion Strength*. Journal of Biological Chemistry (2012).
4. Molecular mechanism for direct actin force-sensing by α-catenin. eLife (2020).
5. Cell-cell junctions as sensors and transducers of mechanical forces. Biochimica et Biophysica Acta (BBA) - Biomembranes (2020).