Résumé :
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Skeletal muscle tissue engineering holds promise for the replacement of muscle due to an injury and for the treatment of muscle diseases. Although RGD substrates have been widely explored in tissue engineering, to date, there is no study investigating the combined effects of RGD nanoscale presentation and matrix stiffness on myogenesis. We use polyelectrolyte multilayer films (PEM) with tunable mechanical properties and functionalized with an RGD-containing peptide derived from type I collagen, one of the key components of muscle ECM, to influence the cell fate of skeletal muscle progenitors by stimulating them mechanically and/or biochemically via cell surface receptors such as integrins. Our results showed that RGD presentation on soft films and film stiffness could both induce cell adhesion, though involved integrins were different. Moreover, soft RGD-presenting films appeared as being appropriate for myogenic differentiation of C2C12 myoblasts, while stiff films increased cell migration, proliferation and inhibited myogenic differentiation. The differences of cell behavior seem to be dependent on Rho/ROCK signaling pathway, which appeared highly regulated by the combination of film stiffness and RGD peptide. Our model films allowed seeing how such important events in myogenesis like adhesion, migration, proliferation, myogenin expression and fusion are regulated by the combination of substrate elasticity and presence of an adhesive ligand.
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