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Updated: Oct 14, 2025

Assessment of Dictyostelium discoideum Response to Acute Mechanical Stimulation
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Clathrin-coated structures support 3D directed migration through local force transmission.

Enzo Bresteau1, Nadia Elkhatib1, Francesco Baschieri1

  • 1Inserm U1279, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.

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Recently identified tubular clathrin/AP-2 lattices (TCALs) mechanically control cell migration. Ligand binding to collagen fibers increases TCALs, directing cell movement along these fibers in 3D environments.

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Area of Science:

  • Cell biology
  • Biophysics
  • Biochemistry

Background:

  • Cell migration is crucial for development and disease, involving sensing biochemical and mechanical cues.
  • Clathrin-coated structures (CCSs) are involved in cellular processes, but their role in mechanical force generation during migration is less understood.

Purpose of the Study:

  • To investigate the role of tubular clathrin/AP-2 lattices (TCALs) in mechanically controlling directed cell migration in 3D environments.
  • To understand how ligand-decorated collagen fibers influence TCAL formation and force distribution.

Main Methods:

  • Utilized engineered, mixed collagen networks to study cell migration.
  • Observed TCALs formation and accumulation in response to ligand-decorated collagen fibers.
  • Investigated the dependence of these effects on ligand receptors and signaling pathways.

Main Results:

  • TCALs, a subset of CCSs, were found to pinch collagen fibers and mechanically control directed migration.
  • Ligands like epidermal growth factor or low-density lipoprotein on collagen fibers promoted local TCAL nucleation and accumulation.
  • This mechanism selectively increased local forces on ligand-decorated fibers, steering cell migration.
  • The observed effects were dependent on ligand receptors but not on downstream signaling events.

Conclusions:

  • Ligand-regulated, local TCAL accumulation results in asymmetric force distribution.
  • TCALs preferentially accumulate along ligand-decorated fibers, steering cell migration in 3D.
  • This provides a novel mechanism for how cells orient their migration in complex 3D environments.