Clathrin-coated structures support 3D directed migration through local force transmission

Bresteau, E., Elkhatib, N., Baschieri, F., Bellec, K. , Guérin, M. and Montagnac, G. (2021) Clathrin-coated structures support 3D directed migration through local force transmission. Science Advances, 7(45), eabf4647. (doi: 10.1126/sciadv.abf4647)

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Migrating cells navigate in complex environments through sensing and interpreting biochemical and/or mechanical cues. Here, we report that recently identified tubular clathrin/AP-2 lattices (TCALs), a subset of clathrin-coated structures (CCSs) that pinch collagen fibers, mechanically control directed migration along fibers decorated with ligands of CCS cargoes in three-dimensional (3D) environments. We observed that epidermal growth factor or low-density lipoprotein bound to collagen fibers leads to increased local nucleation and accumulation of TCALs. By using engineered, mixed collagen networks, we demonstrate that this mechanism selectively increases local forces applied on ligand-decorated fibers. We show that these effects depend on the ligand’s receptors but do not rely on their ability to trigger signaling events. We propose that the preferential accumulation of TCALs along ligand-decorated fibers steers migration in 3D environments. We conclude that ligand-regulated, local TCAL accumulation results in asymmetric force distribution that orients cell migration in 3D environments.

Item Type:Articles
Additional Information:Funding: Core funding for this work was provided by the Gustave Roussy Institute and the Inserm, and additional support was provided by grants from ATIP/Avenir Program, la Fondation ARC pour la Recherche sur le cancer, Le Groupement des Entreprises Françaises dans la LUtte contre le Cancer (GEFLUC), Institut Nationale du Cancer (INCA 2018-1-PL BIO-02-IGR-1), and the Fondation pour la Recherche Médicale (FRM DEQ20180339205) to G.M.
Glasgow Author(s) Enlighten ID:Bellec, Miss Karen
Authors: Bresteau, E., Elkhatib, N., Baschieri, F., Bellec, K., Guérin, M., and Montagnac, G.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
Published Online:05 November 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Science Advances 7(45): eabf4647
Publisher Policy:Reproduced under a Creative Commons licence

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