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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Sorting of cadherin–catenin-associated proteins into individual clusters
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 by
- Award ID(s):
- 1914542
- NSF-PAR ID:
- 10276224
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 118
- Issue:
- 29
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- Article No. e2105550118
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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