4.8 Article

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

Journal

SCIENCE ADVANCES
Volume 7, Issue 45, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abf4647

Keywords

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Funding

  1. Gustave Roussy Institute
  2. Inserm
  3. ATIP/Avenir Program
  4. la Fondation ARC pour la Recherche sur le cancer
  5. Le Groupement des Entreprises Francaises dans la LUtte contre le Cancer (GEFLUC)
  6. Institut Nationale du Cancer [INCA 2018-1-PL BIO-02-IGR-1]
  7. Fondation pour la Recherche Medicale [FRM DEQ20180339205]
  8. grant Taxe d'apprentissage Gustave Roussy-2016-EB

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This study reveals that tubular clathrin/AP-2 lattices (TCALs) play a mechanical role in controlling directed cell migration along fibers decorated with specific ligands in three-dimensional environments. The mechanism involves increasing local forces on ligand-decorated fibers, which is dependent on the ligand's receptors but does not require signaling events to occur. This preferential accumulation of TCALs along ligand-decorated fibers results in asymmetric force distribution that guides cell migration in 3D environments.
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.

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