Shear sensor mechano-signaling determines tendon stiffness and human jumping performance
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Fabian Simone Passini, Patrick K. Jaeger, Aiman S. Saab, Shawn Hanlon, Matthias Arlt, Kim David Ferrari, Nicole Chittim, Dominik Haenni, Sebastiano Caprara, Maja Bollhalder, Aron Horvath, Tobias Goetschi (+8 others)
2020
Abstract
<jats:title>Abstract</jats:title>
Tendons enable movement by transferring muscle forces to the skeleton, and athletic performances critically rely on mechanically-optimized tendons. How load-bearing structures of tendon sense and adapt to physical demands is an open question of central importance to musculoskeletal medicine and human sports performance. Here, with calcium imaging in tendon explants and primary tendon cells we characterized how tenocytes detect mechanical forces and determined collagen fiber-sliding-induced shear stress as a key stimulus. CRISPR/Cas9 screening in human and rat tenocytes identified PIEZO1 as the crucial shear sensor. In rodents, elevated mechano-signaling increased tendon stiffness and strength both <jats:italic>in vitro</jats:italic> by pharmacological channel activation and <jats:italic>in vivo</jats:italic> by a <jats:italic>Piezo1</jats:italic> gain-of-function mutation. Strikingly, humans carrying the <jats:italic>PIEZO1</jats:italic> gain-of-function E756del mutation revealed a 16% average increase in normalized jumping height, with more effective storage of potential energy released during dynamic jumping maneuvers. We propose that PIEZO1-mediated mechano-signaling regulates tendon stiffness and impacts human athletic performance.
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Date 2020-11-10
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