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Updated: Mar 24, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
β3 integrin-mediated spreading induced by matrix-bound BMP-2 controls Smad signaling in a stiffness-independent
Laure Fourel1, Anne Valat1, Eva Faurobert2
1Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 5284, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France Centre National de la Recherche Scientifique UMR 5628, Laboratoire des Matériaux et du Génie Physique, Institute of Technology, 38016 Grenoble, France.
Abstract:
Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin-dependent C2C12 cell spreading by overriding the soft signal of the biomaterial and impacting actin organization and adhesion site dynamics. In turn, αvβ3 integrin is required to mediate BMP-2-induced Smad signaling through a Cdc42-Src-FAK-ILK pathway. β3 integrin regulates a multistep process to control first BMP-2 receptor activity and second the inhibitory role of GSK3 on Smad signaling. Overall, our results show that BMP receptors and β3 integrin work together to control Smad signaling and tensional homeostasis, thereby coupling cell adhesion and fate commitment, two fundamental aspects of developmental biology and regenerative medicine.
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