Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts

Area of Science:

• Cell Biology
• Biophysics
• Cytoskeleton Dynamics

Background:

• Mesenchymal cell migration involves coordinated actin and microtubule networks for protrusion, adhesion, and contraction.
• Collective migration relies on acto-myosin networks in leader cells to generate traction forces transmitted to follower cells.

Purpose of the Study:

• To investigate the role of intermediate filaments (IFs) in regulating collective directed migration of primary astrocytes.
• To elucidate how IFs, including vimentin, glial fibrillary acidic protein, and nestin, influence cytoskeletal dynamics and force distribution during migration.

Main Methods:

• In vitro wound healing assay to induce astrocyte polarization and collective migration.
• Analysis of the interplay between intermediate filaments, actin-myosin network, focal adhesions, and adherens junctions.

Main Results:

• The intermediate filament (IF) network controls force distribution in migrating astrocyte monolayers.
• IFs, with the linker plectin, organize the acto-myosin network, promoting actin-driven treadmilling of adherens junctions for leader cell polarization.
• IFs modulate focal adhesion dynamics and limit their mechanical coupling to the acto-myosin network.

Conclusions:

• Intermediate filaments promote collective directed migration in astrocytes.
• IFs restrict traction force generation to leader cell fronts, preventing aberrant forces in followers.
• IFs contribute to maintaining lateral cell-cell interactions crucial for collective movement.