Force-dependent actin filament-binding by α-catenin recorded with the C-Trap®

A recent publication in the journal eLife describes a multidisciplinary study evaluating how the mechanical properties of actin filaments regulate the binding of associated proteins. Specifically, the researchers used the C-Trap® to demonstrate how applied forces on actin filaments enhance binding of cell–cell adhesion protein α-catenin, but not its homolog vinculin.

The findings reveal previously unknown mechanisms by which mechanical cues trigger signaling pathways related to intercellular adhesion, causing several chronic conditions when aberrant.

Mei et al. investigated force-dependent interactions between actin filaments and the actin-binding domains of α-catenin and vinculin through an optical tweezers strategy. In essence, they captured actin filaments between two optically trapped beads, stretched the filament at different forces, and assessed the association of fluorescently tagged actin-binding domains in response to the mechanical manipulation. The latter measurements could be performed by recording the interactions with the correlated confocal microscopy function.

The researchers found that tension on the actin filaments enhances the binding of α-catenin, suggesting that the protein can sense myosin-induced contraction of the actin filaments. By contrast, they did not find the same contraction-dependent binding properties in the vinculin protein. Further validation through cryo-electron microscopy and protein truncation assays revealed that α-catenin’s force-detection on actin fibers resided from its distinct C-terminal extension.

Thus, measuring forces on actin filaments – which are associated with filament polymerization and architecture – paved the way to identify characteristic features of closely related actin-binding proteins.

“We propose this force-activated [fibrous] F actin binding could play an important role in the formation and reinforcement of cell-cell adhesion complexes, facilitating mechanically regulated interactions between α-catenin and actomyosin cables tuned for high sensitivity to motor-generated forces,” the authors concluded.

“Defects in mechanotransduction are associated with numerous diseases, including muscular dystrophies, cardiomyopathies, and metastatic cancer, yet therapeutics which specifically target these pathways are largely absent due to our ignorance of the mechanisms that transduce mechanical signals through the cytoskeleton,”

Congratulations to Lin Mei and all the other authors involved in this study for this exciting publication!

For more information, read the full article published in the journal eLife titled “Molecular mechanism for direct actin force-sensing by α-catenin“.

Are you interested in using dynamic single-molecule tools like the C-Trap® for your research? Feel free to contact us for more information, a demo, or a quote.

 

Want to learn more about this application and our solutions?

Cellular Structure and Transport

Study the activity and mechanical properties of cytoskeleton filaments and their motors.

Optical Tweezers and Fluorescence Microscopy

Technology

The combination of optical tweezers and fluorescence microscopy allows for simultaneous manipulation and visualization of molecular interactions in real-time.

Solutions

C-Trap

Optical Tweezers and Fluorescence Microscopy

m-Trap

Optical Tweezers

Take your research to the next level.

Get exclusive news on the latest products, single-molecule events and breakthrough science.

Newsletter pop up
By clicking the subscribe button you agree to LUMICKS’ privacy policy.