Key result
Cell activation switches titin to a mechanical rectifier with ~3 pN/nm stiffness.
Why the study?
The role of titin at physiological sarcomere length is unclear.
This study identifies titin as a mechanical rectifier in active skeletal muscle, providing a biophysical basis for force transmission and mechanosensing activation of thick filaments.
Titin rectification during activation may refine sarcomere force models; leaves open relevance to human cardiac titin mechanics.
Titin is a molecular spring in parallel with myosin motors in each muscle half-sarcomere, responsible for passive force development at sarcomere length (SL) above the physiological range (>2.7 μm). The role of titin at physiological SL is unclear and is investigated here in single intact muscle cells of the frog ( Rana esculenta ), by combining half-sarcomere mechanics and synchrotron X-ray diffraction in the presence of 20 μM para-nitro-blebbistatin, which abolishes the activity of myosin motors and maintains them in the resting state even during activation of the cell by electrical stimulation. We show that, during cell activation at physiological SL, titin in the I-band switches from an SL-dependent extensible spring (OFF-state) to an SL-independent rectifier (ON-state) that allows free shortening while resisting stretch with an effective stiffness of ~3 pN nm −1 per half-thick filament. In this way, I-band titin efficiently transmits any load increase to the myosin filament in the A-band. Small-angle X-ray diffraction signals reveal that, with I-band titin ON, the periodic interactions of A-band titin with myosin motors alter their resting disposition in a load-dependent manner, biasing the azimuthal orientation of the motors toward actin. This work sets the stage for future investigations on scaffold and mechanosensing-based signaling functions of titin in health and disease.
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Squarci et al. (2023) studied this question. Electrical stimulation and mechanical force steps in the presence of para-nitro-blebbistatin vs. Resting muscle cell state was evaluated on Half-sarcomere mechanical responses and structural changes via X-ray diffraction. During cell activation at physiological sarcomere length, I-band titin switches from an extensible spring to a mechanical rectifier with an effective stiffness of ~3 pN nm−1.
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