Differential bioactivity of four BMP-family members as function of biomaterial stiffness

Adrià Sales (1, 2) , Valia Khodr (1, 2) , Paul Machillot (1, 2) , Line Chaar (3) , Laure Fourel (3, 4) , Amaris Guevara-Garcia (3, 1) , Elisa Migliorini (1, 2) , Corinne Albigès-Rizo (3) , Catherine Picart (1)

1 BRM - Biomimétisme et Médecine Régénératrice
2 LMGP - Laboratoire des matériaux et du génie physique
3 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
4 IUF - Institut universitaire de France

While a soft film itself is not able to induce cell spreading, BMP-2 presented via such soft film (so called “matrix-bound BMP-2”) was previously shown to trigger cell spreading, migration and downstream BMP-2 signaling. Here, we used thin films of controlled stiffness presenting matrix-bound BMPs to study the effect of four BMP members (BMP-2, 4, 7, 9) on cell adhesion and differentiation of skeletal progenitors. We performed automated high content screening of cellular responses, including cell number, cell spreading area, SMAD phosphorylation and alkaline phosphatase activity. We revealed that the cell response to bBMPs is BMP-type specific and involved certain BMP receptors and beta chain integrins. In addition, this response is stiffness-dependent for several receptors. The basolateral presentation of the BMPs allowed us to discriminate the specificity of cellular response and the role of type I and II BMP receptors and of β integrins in a BMPtype and stiffness-dependent manner. Notably, the role of BMP-2 and BMP-4 were found to have distinct roles, while ALK5, previously known as a TGF-β receptor was revealed to be involved in the BMP-pathway.

Domaines: Biotechnologies; Biomatériaux

Adrià Sales, Valia Khodr, Paul Machillot, Line Chaar, Laure Fourel, et al.. Differential bioactivity of four BMP-family members as function of biomaterial stiffness. Biomaterials, 2022, ⟨10.1016/j.biomaterials.2022.121363⟩. ⟨hal-03149898v2⟩