Ladoux/Mege – Extracellular-matrix mediated stresses spatially bias myoblast fusion and myotube growth

The Ladoux/Mège Lab published a new article in Nature Communications:

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

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.

Le Toquin Y, Dubey S, Ardaševa A, Balasubramaniam L, Delaune E, Morin V, Doostmohammadi A, Marcelle C, Ladoux B. Extracellular-matrix mediated stresses spatially bias myoblast fusion and myotube growth. Nat Commun. 2026 Aug 22;17(1):10057. doi: 10.1038/s41467-026-76967-6. PMID: 42768042; PMCID: PMC13594122.