The shaping of a multicellular body and repair of adult tissues require fine-tuning of cell adhesion, cell mechanics, and intercellular transmission of mechanical load. Adherens junctions (AJs) are the major intercellular junctions by which cells sense and exert mechanical force on each other. However, how AJs adapt to mechanical stress and how this adaptation contributes to cell-cell cohesion and eventually to tissue-scale dynamics and mechanics remains largely unknown. Here, by analyzing the tension-dependent recruitment of vinculin, α-catenin, and F-actin as a function of stiffness, as well as the dynamics of GFP-tagged wild-type and mutated α-catenins, altered for their binding capability to vinculin, we demonstrate that the force-dependent binding of vinculin stabilizes α-catenin and is responsible for AJ adaptation to force. Challenging cadherin complexes mechanical coupling with magnetic tweezers, and cell-cell cohesion during collective cell movements, further highlight that tension-dependent adaptation of AJs regulates cell-cell contact dynamics and coordinated collective cell migration. Altogether, these data demonstrate that the force-dependent α-catenin/vinculin interaction, manipulated here by mutagenesis and mechanical control, is a core regulator of AJ mechanics and long-range cell-cell interactions.
|Number of pages||9|
|Journal||Molecular Biology of the Cell|
|Publication status||Published - 15 Feb 2018|
Bibliographical noteFunding Information:
This work was supported by grants from the Centre National de la Recherche Scientifique (CNRS), Université Paris-Diderot (R.M.M., B.L.), NUS-SPC (National University of Singapore-Université Sorbonne-Paris-Cité), and Projet International de Coopération Scienti-fique (PICS) CNRS programmes (R.M.M.), Fondation ARC pour la recherche sur le cancer (R.M.M.), the Human Frontier Science Program (Grant no. RPG0040/2012; B.L. and R.M.M.), the LABEX “Who am I?,” and Agence Nationale de la Recherche (ANR 2010 Blan1515). B.L. is supported by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC [European Research Council] Grant agreement no. 617233) and the Mechanobiology Institute. R.S. has been supported by a C’nano program Région Ile de France doctoral fellowship and Fondation pour la Recherche Médicale (FRM) (FDT20140930851). We acknowledge the IJM ImagoSeine Imaging Facility, member of the France BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04, “Investments of the future”).
© 2018 Seddiki et al.