Mechanochemical waves in focal adhesions during cell migration

Area of Science:

• Cell Biology
• Biophysics
• Molecular Mechanotransduction

Background:

• Focal adhesions (FAs) are critical for cell migration, linking the extracellular matrix (ECM) to intracellular signaling.
• FA kinase (FAK) is a key signaling molecule activated at FAs, but its activation mechanism by mechanical forces at single FAs is unclear.

Purpose of the Study:

• To investigate the real-time activation mechanism of FAK in response to mechanical forces at individual focal adhesions.
• To elucidate the spatiotemporal relationship between force and FAK activity during FA dynamics.

Main Methods:

• Micropillar-based force microscopy to measure traction forces at single FAs.
• Förster Resonance Energy Transfer (FRET) biosensors to monitor FAK activity in real-time.
• Atomistic molecular dynamics simulations to explore force-induced FAK activation mechanisms.

Main Results:

• Demonstrated an oscillatory temporal coupling between traction force and FAK activity in high-tension FAs.
• Showed that mechanical force precedes FAK activation, guiding focal adhesion turnover.
• Revealed a force-induced mechanism where traction disrupts autoinhibitory FAK interactions, enabling catalytic activity.

Conclusions:

• Mechanical forces directly regulate FAK activation at the single-molecule level.
• FAK activation is spatiotemporally integrated with mechanical forces to drive cell migration.
• Findings provide mechanistic insights into mechanotransduction at focal adhesions.