(776f) Mechano-Transduction Pathway Interference with BMP-2 Signaling Cascade

The bone morphogenetic proteins (BMP) growth factors are essential signaling molecules in embryogenesis, tissue regeneration or cancer metastasis. Until now, the cellular effects of these proteins have mostly been investigated by adding them in solution in the cell culture medium even though growth factors are naturally not free to diffuse and are rather bound to ECM components including proteins and polysaccharides. In this work, we design a new biomimetic nanoassembly based on polyelectrolyte multilayer film made of a polypeptide and of hyaluronan which combines both matrix-bound presentation of growth factor bone morphogenetic protein 2 (BMP2) and modulation of the material’s mechanical properties. We investigated the interplay between the stiffness of a biomaterial and the matrix-bound presentation of the growth factor BMP2 and its impact on cellular processes. Whereas C2C12 myoblast cells are round and poorly spread on soft films, cells displayed an increase of spreading and migration. By using a combined set of techniques including SiRNA strategy and pharmacological approach, we study how the mechano-transduction pathway can potentially interfere with the BMP-2 signalling cascade. We demonstrated a crosstalk between specific integrin and BMP2 receptors. Our results pointed out that signaling can be enhanced by the spatial association of integrin and BMP2 receptors.