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bioRxiv · 10.64898/2026.05.18.725456

Mechanical Loading Induces the Radial Growth of Myofibrils and Myofibrillogenesis via an mTORC1-Dependent Mechanism

Flynn, C. G. K.·Sayed, R. K. A.·Lange, A. N.·Zhu, W. G.·Hornberger, T.
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Abstract

Increased mechanical loading induces skeletal muscle growth and, at the ultrastructural level, promotes myofibrillogenesis and the radial growth of myofibrils. However, the mechanisms regulating these ultrastructural adaptations are not known. Here, we sought to determine whether the mechanistic target of rapamycin complex 1 (mTORC1) regulates these processes. To accomplish this, muscle-specific, tamoxifen-inducible raptor knockout (iRAmKO) mice were used to inhibit signaling through mTORC1, and growth was induced with a model of chronic mechanical overload (MOV). Using a next-generation fluorescence imaging pipeline for ultrastructural analyses, we found that mTORC1 is a critical regulator of the myofibrillogenesis and radial growth of myofibrils that occur in response to MOV. Together with other recent advances in the field, we propose a model in which mTORC1 acts as a gatekeeper that permits the retention, rather than the synthesis, of proteins that drive the ultrastructural adaptations.

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Flynn, C. G. K., Sayed, R. K. A., Lange, A. N., Zhu, W. G., Hornberger, T.. 2026-05-20. Mechanical Loading Induces the Radial Growth of Myofibrils and Myofibrillogenesis via an mTORC1-Dependent Mechanism. https://doi.org/10.64898/2026.05.18.725456

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