Coupling during collective cell migration is controlled by a vinculin mechanochemical switch

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Collective cell migration is crucial for development and disease, yet the interplay between mechanical forces and biochemical regulation remains poorly understood.
• Understanding how cells coordinate movement is essential for addressing developmental abnormalities and pathological conditions.

Purpose of the Study:

• To investigate the mechanical functions and biochemical regulation of the linker protein vinculin in collective cell migration.
• To elucidate the regulatory mechanisms controlling cell-cell mechanical coupling and coordination.

Main Methods:

• Utilized Förster resonance energy transfer (FRET)-based biosensors to probe vinculin's mechanical states and biochemical regulation.
• Employed molecular-scale modeling to understand the relationship between vinculin loadability and system friction.
• Perturbed the identified regulatory switch to observe effects on cell migration dynamics.

Main Results:

• Identified a regulatory switch that toggles vinculin between loadable and unloadable states.
• Demonstrated that altering this switch affects cell speed and coordination, indicating changes in system friction.
• Molecular modeling revealed that increased loadable vinculin enhances friction through catch bond engagement.

Conclusions:

• Revealed a novel regulatory switch controlling cell coupling during collective cell migration.
• Established a paradigm linking biochemical regulation, altered mechanical properties (friction), and cell behavior.
• Provides new insights into the biophysical mechanisms governing coordinated cell movement.