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The multiple roles of titin in muscle contraction and force production

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Abstract

Titin is a filamentous protein spanning the half-sarcomere, with spring-like properties in the I-band region. Various structural, signaling, and mechanical functions have been associated with titin, but not all of these are fully elucidated and accepted in the scientific community. Here, I discuss the primary mechanical functions of titin, including its accepted role in passive force production, stabilization of half-sarcomeres and sarcomeres, and its controversial contribution to residual force enhancement, passive force enhancement, energetics, and work production in shortening muscle. Finally, I provide evidence that titin is a molecular spring whose stiffness changes with muscle activation and actin–myosin-based force production, suggesting a novel model of force production that, aside from actin and myosin, includes titin as a “third contractile” filament. Using this three-filament model of sarcomeres, the stability of (half-) sarcomeres, passive force enhancement, residual force enhancement, and the decrease in metabolic energy during and following eccentric contractions can be explained readily.

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  1. Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, AB, T2N 1N4, Canada

    Walter Herzog

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Ethics approvals for all experiments described in this study were obtained by the Life Sciences and Animal Research Ethics Commitee of the University of Calgary.

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Herzog, W. The multiple roles of titin in muscle contraction and force production. Biophys Rev 10, 1187–1199 (2018). https://doi.org/10.1007/s12551-017-0395-y

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