Journal
BIOPHYSICAL JOURNAL
Volume 111, Issue 5, Pages 1044-1052Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2016.06.027
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Funding
- National Research Foundation
- Competitive Research Program grant [CRP001-084]
- National University of Singapore
- Singapore through the Mechanobiology Institute
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Mechanotransduction at E-cadherin junctions has been postulated to be mediated in part by a force-dependent conformational activation of alpha-catenin. Activation of alpha-catenin allows it to interact with vinculin in addition to F-actin, resulting in a strengthening of junctions. Here, using E-cadherin adhesions reconstituted on synthetic, nanopatterned membranes, we show that activation of alpha-catenin is dependent on E-cadherin clustering, and is sustained in the absence of mechanical force or association with F-actin or vinculin. Adhesions were formed by filopodia-mediated nucleation and micron-scale assembly of E-cadherin clusters, which could be distinguished as either peripheral or central assemblies depending on their relative location at the cell-bilayer adhesion. Whereas F-actin, vinculin, and phosphorylated myosin light chain associated only with the peripheral assemblies, activated alpha-catenin was present in both peripheral and central assemblies, and persisted in the central assemblies in the absence of actomyosin tension. Impeding filopodia-mediated nucleation and micron-scale assembly of E-cadherin adhesion complexes by confining the movement of bilayer-bound E-cadherin on nanopatterned substrates reduced the levels of activated alpha-catenin. Taken together, these results indicate that although the initial activation of alpha-catenin requires micron-scale clustering that may allow the development of mechanical forces, sustained force is not required for maintaining alpha-catenin in the active state.
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