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1. Push-pull mechanics of E-cadherin ectodomains

   K. Nagendra, A. Izzet (April 2023, Biophysical journal)

   E-cadherin plays a central role in cell-cell adhesion. The ectodomains of wild type cadherins form a crystalline- like two dimensional lattice in cell-cell interfaces mediated by both trans (apposed cell) and cis (same cell) interactions. In addition to these extracellular forces, adhesive strength is further regulated by cytosolic phenomena involving 𝛼 and 𝛽- catenin–mediated interactions between cadherin and the actin cytoskeleton. Cell-cell adhesion can be further strengthened under tension through mechanisms that have not been definitively characterized in molecular detail. Here we quantitatively determine the role of the cadherin ectodomain in mechanosensing. To this end, we devise an E-cadherin-coated emulsion system, in which droplet surface tension is balanced by protein binding strength to give rise to stable areas of adhesion. To reach the honeycomb/cohesive limit, an initial emulsion compression by centrifugation facilitates E-cadherin trans-binding, while a high protein surface concentration enables the cis-enhanced stabilization of the interface. We observe an abrupt concentration dependence on recruitment into adhesions of constant crystalline density, reminiscent of a first-order phase transition. Removing the lateral cis-interaction with a "cis mutant" shifts this transition to higher surface densities leading to denser, yet weaker adhesions. In both proteins, the stabilization of progressively larger areas of deformation can be rationalized by a stiffening catch-bond, whose strength increases with tension. This catch bond may well correspond to one that has been identified in the cadherin “X-dimer". 

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2. Cadherin genes and evolutionary novelties in the octopus

   https://doi.org/10.1016/j.semcdb.2017.06.007  

   Wang, Z. Yan; Ragsdale, Clifton W. (September 2017, Seminars in Cell & Developmental Biology)
3. Computational model of E-cadherin clustering under force

   https://doi.org/10.1016/j.bpj.2021.10.018  

   Chen, Yang; Brasch, Julia; Harrison, Oliver J.; Bidone, Tamara C. (November 2021, Biophysical Journal)
4. Sorting of cadherin–catenin-associated proteins into individual clusters

   https://doi.org/10.1073/pnas.2105550118  

   Troyanovsky, Regina B.; Sergeeva, Alina P.; Indra, Indrajyoti; Chen, Chi-Shuo; Kato, Rei; Shapiro, Lawrence; Honig, Barry; Troyanovsky, Sergey M. (July 2021, Proceedings of the National Academy of Sciences)

   The cytoplasmic tails of classical cadherins form a multiprotein cadherin–catenin complex (CCC) that constitutes the major structural unit of adherens junctions (AJs). The CCC in AJs forms junctional clusters, “E clusters,” driven bycisandtransinteractions in the cadherin ectodomain and stabilized by α-catenin–actin interactions. Additional proteins are known to bind to the cytoplasmic region of the CCC. Here, we analyze how these CCC-associated proteins (CAPs) integrate into cadherin clusters and how they affect the clustering process. Using a cross-linking approach coupled with mass spectrometry, we found that the majority of CAPs, including the force-sensing protein vinculin, interact with CCCs outside of AJs. Accordingly, structural modeling shows that there is not enough space for CAPs the size of vinculin to integrate into E clusters. Using two CAPs, scribble and erbin, as examples, we provide evidence that these proteins form separate clusters, which we term “C clusters.” As proof of principle, we show, by using cadherin ectodomain monoclonal antibodies (mAbs), that mAb-bound E-cadherin forms separate clusters that undergotransinteractions. Taken together, our data suggest that, in addition to its role in cell–cell adhesion, CAP-driven CCC clustering serves to organize cytoplasmic proteins into distinct domains that may synchronize signaling networks of neighboring cells within tissues. 

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5. Unraveling the mechanism of the cadherin-catenin-actin catch bond

   https://doi.org/10.1371/journal.pcbi.1006399  

   Adhikari, Shishir; Moran, Jacob; Weddle, Christopher; Hinczewski, Michael; MacKerell, Alexander (August 2018, PLOS Computational Biology)