Talin folding as the tuning fork of cellular mechanotransduction

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 35; pp. 21346 - 21353
• Main Authors: Tapia-Rojo, Rafael, Alonso-Caballero, Álvaro, Fernández, Julio M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01.09.2020
• Subjects: Bandpass filters; Biological Sciences; Folding; Frequency dependence; Frequency ranges; Magnetic tape; Mechanical stimuli; Mechanotransduction; Mechanotransduction, Cellular; Noise; Physical Sciences; Protein Domains; Protein Folding; Proteins; Single Molecule Imaging; Stochastic resonance; Talin; Talin - physiology; stochastic resonance; protein folding; magnetic tweezers; talin
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2004091117

Cells continually sample their mechanical environment using exquisite force sensors such as talin, whose folding status triggers mechanotransduction pathways by recruiting binding partners. Mechanical signals in biology change quickly over time and are often embedded in noise; however, the mechanics of force-sensing proteins have only been tested using simple force protocols, such as constant or ramped forces. Here, using our magnetic tape head tweezers design, we measure the folding dynamics of single talin proteins in response to external mechanical noise and cyclic force perturbations. Our experiments demonstrate that talin filters out external mechanical noise but detects periodic force signals over a finely tuned frequency range. Hence, talin operates as a mechanical band-pass filter, able to read and interpret frequency-dependent mechanical information through its folding dynamics. We describe our observations in the context of stochastic resonance, which we propose as a mechanism by which mechanosensing proteins could respond accurately to force signals in the naturally noisy biological environment.