Myosin forces remodel F-actin for mechanosensitive protein recognition

Area of Science:

• Cellular mechanics
• Biophysics
• Molecular biology

Background:

• Cells interact with their environment via cytoskeleton-linked adhesions.
• Myosin motor proteins generate forces crucial for mechanical signal transduction.
• The structural mechanisms underlying this process remain largely unknown.

Purpose of the Study:

• Investigate how myosin forces alter actin filament structure.
• Determine how these structural changes affect the binding of mechanosensitive proteins like α-catenin.
• Elucidate the structural mechanisms of mechanical signal transduction in cells.

Main Methods:

• Correlative cryo-fluorescence microscopy and cryo-electron tomography.
• Development of a reconstitution system for visualizing F-actin under myosin forces.
• Cryo-electron microscopy and molecular simulations.

Main Results:

• Myosin forces induce sinusoidal curvature and supercoiling in F-actin.
• These F-actin structures exhibit asymmetric remodelling of their helical lattice.
• α-catenin binds cooperatively to these deformed F-actin structures, preferentially at interfaces with extended inter-subunit distances.

Conclusions:

• Myosin-generated forces deform F-actin into a specific conformational landscape.
• This landscape is recognized and modulated by α-catenin.
• Provides direct structural insight into force transduction at the cytoskeleton-adhesion interface.