Mechanical stresses govern myoblast fusion and myotube growth

Le Toquin, Y.; Dubey, S.; Ardaseva, A.; Balasubramaniam, L.; Delaune, E.; Morin, V.; Doostmohammadi, A.; Marcelle, C.; Ladoux, B.

doi:10.1101/2024.11.22.624831

bioRxiv · 10.1101/2024.11.22.624831

Mechanical stresses govern myoblast fusion and myotube growth

Le Toquin, Y.·Dubey, S.·Ardaseva, A.·Balasubramaniam, L.·Delaune, E.·Morin, V.·Doostmohammadi, A.·Marcelle, C.·Ladoux, B.

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Abstract

Myoblast fusion into multinucleated myotubes is essential for skeletal muscle development and repair, yet how tissue-scale mechanics contributes to this process remains poorly understood. Here, we show that primary myoblasts behave as an evolving active nematic system in which actomyosin-dependent stresses, extracellular-matrix (ECM) remodeling and fusion-driven myotube growth are dynamically coupled. As myoblasts fuse into elongated myotubes, orientational order increases and the nematic field is progressively reshaped. We identify a strong coupling between cellular and ECM nematic organization, whereby cytoskeleton-dependent ECM remodeling stabilizes topological defects and reinforces their associated stress patterns. Fusion events preferentially accumulate near comet-shaped +1/2 defects, which correspond to regions of high compressive stress predicted by our theoretical model. Our findings support a model in which the intrinsic fusion machinery provides fusion competence, while ECM-stabilized nematic stress patterns spatially bias the localization of fusion events. Fusion-driven myotube growth then feeds back on the mechanical landscape, increasing nematogen length and stress magnitude. Together, these results reveal a self-reinforcing biomechanical mechanism that contributes to the organization of myoblast fusion and myotube growth, with potential relevance for developmental and regenerative morphogenesis.

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Le Toquin, Y., Dubey, S., Ardaseva, A., Balasubramaniam, L., Delaune, E., Morin, V., Doostmohammadi, A., Marcelle, C., Ladoux, B.. 2024-11-23. Mechanical stresses govern myoblast fusion and myotube growth. https://doi.org/10.1101/2024.11.22.624831

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