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Biomimetic film of controlled stiffness to study protein bioactivity toward human cells

We used biomimetic films of controlled stiffness presenting matrix-bound BMPs (Bone Morphogenetic Proteins) to study the effect of four BMPs on cell adhesion and differentiation of skeletal progenitors. This is the first study of cell signaling using the biomimetic films, where unsuspected effects of BMP proteins that were previously masked by cell culture conditions are revealed thanks to the biomaterial of controlled stiffness.

Published on 9 March 2022
The activity of proteins is generally studied by adding them as soluble protein in the cell culture medium, the cells being themselves grown on glass or plastic surfaces. However, the rigidity of these surfaces affects the cell response. In a their Biomaterials research paper, researchers from the Biomimetism and Regenerative Medicine team (BRM) at the Biology and Biotechnology for Health Laboratory (UMR_S 1292 CEA-Inserm-Université Grenoble Alpes), the Materials and Engineering Physics Laboratory (LMGP, CNRS-Université Grenoble Alpes) and the Institute for the Advancement of Biosciences (IAB, CNRS-Inserm-Université Grenoble Alpes) have successfully tested a patented process for studying the biological activity of proteins delivered to cells via soft and stiff biomimetic films.

These self-assembled films, which are less than two micrometers thick, are composed of biopolymers present in the extracellular matrix of our body. The films of controlled rigidity are deposited using an automated process at the bottom of multi-well cell culture microplates. The team used this process to study the biological activity of four proteins of the bone morphogenetic proteins (BMP) family, involved in bone and muscle formation. They discovered the specificity of some BMPs in cell adhesion and cell spreading. These properties could not be observed on a rigid support. Many cell and developmental biology experiments aimed at studying the role of BMPs in physiological and pathological conditions may be revisited by delivering BMPs via the biomimetic films of controlled stiffness. Thus, the stiffness control appears to be a major parameter in the study of the biological activity of BMPs. More broadly, this works opens innovative perspectives to study the activity of other proteins or therapeutic molecules.

Example of multi-well plates with flexible films on the bottom.
© Paul Machillot.

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