Mechanosensing through focal adhesion-anchored intermediate filaments

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Integrin-mediated mechanotransduction is crucial for cellular responses to mechanical forces.
• Focal adhesions (FAs) and the actomyosin network are key components of this process.
• The role of vimentin intermediate filaments (IFs) in mechanotransduction remains incompletely understood.

Purpose of the Study:

• To investigate the regulatory role of vimentin IFs in integrin-based mechanotransduction.
• To elucidate the impact of vimentin network integrity on FA dynamics and cell migration.
• To understand the molecular mechanisms linking cytoskeletal tension to cell mechanosensing.

Main Methods:

• Studied fibroblasts with vimentin IFs decoupled from FAs (vimentin-deficient (V0) and plectin-deficient (P0) cells).
• Assessed activation of mechanosensor molecules like FAK and downstream targets (Src, ERK1/2, p38).
• Analyzed FA turnover, cell migration, protrusion formation, and integrin complex characteristics under tension-independent conditions.

Main Results:

• Vimentin IFs are essential for proper FA-associated mechanotransduction.
• Decoupling vimentin IFs from FAs attenuated FAK activation and downstream signaling.
• Reduced cytoskeletal tension in V0 and P0 cells led to impaired directional migration and FA turnover.

Conclusions:

• Vimentin IFs play a previously unrecognized regulatory role in integrin-based mechanotransduction.
• Diminished cytoskeletal tension due to vimentin network defects impairs cell migration and FA dynamics.
• These findings offer insights into cytoskeleton-regulated mechanosensing, crucial for cell movement and tumor progression.