Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Monday Speaker Abstracts

VINCULIN ALLOSTERICALLY ENHANCES FORCE-DEPENDENT BINDING OF ALPHA-E-CATENIN TO F-ACTIN William Weis 1 ; Nicholas Bax 1 ; Derek Huang 1 ; Alexander Dunn 1 ; 1 Stanford University, Stanford, CA, USA The connection of cadherin-based intercellular adhesions and the actomyosin cytoskeleton is a fundamental feature of metazoan tissues. alphaE-catenin, which links the cadherin/beta-catenin complex to F-actin, displays catch bond behavior, such that force applied to the ternary cadherin/beta-catenin/alphaE-catenin complex enhances its lifetime on actin. Mechanical tension also promotes binding of the actin-binding protein vinculin to alphaE-catenin, which is thought to reinforce the cadherin-catenin/actin linkage. Here, we examined the effect of vinculin on binding of the ternary cadherin/beta-catenin/alphaE-catenin complex to actin. Although the actin-binding activity of vinculin likely contributes to junctional strengthening, we find that a vinculin construct lacking its actin-binding domain enhances the lifetime of the cadherin/catenin complex on actin, in a force-dependent manner. Computational modeling suggests that this force-dependent strengthening of individual alphaE-catenin/F-actin bonds results in adhesions with increased resilience to fluctuating loads and higher energetic efficiency in force transmission at cell-cell junctions. Our results demonstrate a form of force-dependent allosteric regulation that may enhance the ability of cells to form robust connections and sense mechanical cues at cell-cell contacts.

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