Genetic and Mechanical Control of Myoblast Fusion. – MyoFuse

During the first 18 months period, significant advances were made on the project.
The teams of FLG and BL developed a miniaturized 3D myotube culture chip with contraction monitoring capacity. This was done by using micropatterned substrate to grow primary myoblasts. Spontaneous contractions in myotubes derived from primary human myoblasts were observed. Analysis of nuclear morphology confirmed a similar organization between obtained myotubes and in vivo myofibers. LMNA-related Congenital Muscular Dystrophy (L-CMD) was modelled with mutant 3D myotubes displaying contractile dysfunction. This technology can thus be used to study contraction characteristics and evaluate how diseases affect muscle organization and force generation. Importantly, it requires significantly fewer starting materials than current systems, which should allow to substantially improve drug screening capability. A paper describing these data was recently submitted for publication (https://www.biorxiv.org/content/10.1101/2021.06.15.448543v3).
The teams of CM and BL have made significant advances in our understanding of the regulation of fusion by mechanical stress. Preliminary data they have obtained using traction force microscopy and live imaging shows that, in vitro, myoblast and myocyte fusion predominantly occurs in regions of increased environmental /cellular stress, which tightly correlate with singularities in cell alignments, also named nematic defects. The results of these analyses have been presented by CM at the Society for Muscle Biology «Frontiers in Myogenesis« International Conference in Costa Rica in November 2021. These results are important, as they show for the first time that mechanical stress (environmental / intra-tissular) could represent an underestimated regulator of myoblast fusion. These results need first to be confirmed. Translation of these results with in vivo context needs to be investigated and tested.
CM team is also investigating the role of putative TGF beta effectors in the regulation of fusion. These are ongoing experiments with no major breakthrough yet.
The experiments that were done during the first 18 months period are in line with the proposed experiments in the research project. Moreover, very significant advances were made in a short time, underlying the originality and high potential of this project

Publication par les équipes de F. Le Grand et B. Ladoux d'un article (Bioengineering a Miniaturized In Vitro 3D Myotube Contraction Monitoring Chip For Modelization of Muscular Dystrophies) pour le moment dans bioRxiv, soumis à Biomaterials.
Présentation par C. Marcelle des données issues de la collaboration CM/BL sur la mécanotransduction à un congrès international (Frontiers in Myogenesis Conference)

Publication par les équipes de F. Le Grand et B. Ladoux d'un article (Bioengineering a Miniaturized In Vitro 3D Myotube Contraction Monitoring Chip For Modelization of Muscular Dystrophies) pour le moment dans bioRxiv, soumis à Biomaterials.
Présentation par C. Marcelle des données issues de la collaboration CM/BL sur la mécanotransduction à un congrès international (Frontiers in Myogenesis Conference)