Extracellular-matrix mediated stresses spatially bias myoblast fusion and myotube growth

Le Toquin Y, Dubey S, Ardaševa A, Balasubramaniam L, Delaune E, Morin V, Doostmohammadi A, Marcelle C, Ladoux B (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 17

Article Number: 10057

Journal Issue: 1

DOI: 10.1038/s41467-026-76967-6

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.

Authors with CRIS profile

Sushil Dubey Lehrstuhl für Biophysik (Alexander von Humboldt-Professur) Benoit Ladoux Lehrstuhl für Biophysik (Alexander von Humboldt-Professur)

Involved external institutions

Niels Bohr Institute / Niels Bohr Institutet DK Denmark (DK) Université Claude Bernard Lyon 1 (UCB) FR France (FR) Université Paris Cité FR France (FR)

How to cite

APA:

Le Toquin, Y., Dubey, S., Ardaševa, A., Balasubramaniam, L., Delaune, E., Morin, V.,... Ladoux, B. (2026). Extracellular-matrix mediated stresses spatially bias myoblast fusion and myotube growth. Nature Communications, 17(1). https://doi.org/10.1038/s41467-026-76967-6

MLA:

Le Toquin, Yoann, et al. "Extracellular-matrix mediated stresses spatially bias myoblast fusion and myotube growth." Nature Communications 17.1 (2026).

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