Molecular mechanism for direct actin force-sensing by α-catenin

Area of Science:

• Cell biology
• Biophysics
• Structural biology

Background:

• The actin cytoskeleton is crucial for mechanical coupling between cells and their microenvironment.
• Force significantly influences actin network architecture and composition.
• The mechanical regulation of protein interactions with actin filaments remains poorly understood.

Purpose of the Study:

• To investigate how forces on actin filaments (F-actin) mechanically regulate the binding of associated proteins.
• To determine if the cell-cell adhesion protein αE-catenin exhibits force-dependent binding to F-actin.
• To elucidate the structural basis for force-modulated protein-actin interactions.

Main Methods:

• Utilized optical trapping to apply precise piconewton forces to F-actin.
• Employed biochemical reconstitution with myosin motor proteins.
• Determined high-resolution structures using cryo-electron microscopy.

Main Results:

• Single piconewton forces applied to F-actin specifically enhance the binding of αE-catenin, but not vinculin.
• Cryo-EM structures reveal unique rearrangements in αE-catenin and vinculin upon F-actin binding.
• The C-terminus of αE-catenin acts as a modular tension sensor, mediating force-activated binding.

Conclusions:

• Piconewton forces on F-actin can enhance protein binding affinity.
• αE-catenin's C-terminus is a novel mechanosensor that detects F-actin tension.
• This force-gated binding mechanism likely regulates cellular adhesion through αE-catenin.