Interplay of Matrix Stiffness and Protein Tethering in Stem Cell Differentiation

By J. Wen, L. Vincent, A. Fuhrmann, Yu Suk Choi, K. Hribar, Hermes Taylor-Weiner, Shaochen Chen, A. Engler. Nature Materials, 2014

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Stem cells regulate their fate by binding to, and contracting against, the extracellular matrix. Recently, it has been proposed that in addition to matrix stiffness and ligand type, the degree of coupling of fibrous protein to the surface of the underlying substrate, that is, tethering and matrix porosity, also regulates stem cell differentiation. By modulating substrate porosity without altering stiffness in polyacrylamide gels, we show that varying substrate porosity did not significantly change protein tethering, substrate deformations, or the osteogenic and adipogenic differentiation of human adipose-derived stromal cells and marrow-derived mesenchymal stromal cells. Varying protein-substrate linker density up to 50-fold changed tethering, but did not affect osteogenesis, adipogenesis, surface-protein unfolding or underlying substrate deformations. Differentiation was also unaffected by the absence of protein tethering. Our findings imply that the stiffness of planar matrices regulates stem cell differentiation independently of protein tethering and porosity.

Subfields: Biomedical Engineering, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5a68f530f0b44d422c565b9d834ec16e6fb0571e

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Citations in the corpus

A Review of Cell Adhesion Studies for Biomedical and Biological Applications (2015, background): “[53] reported stem cell differentiation was regulated by the stiffness of planar matrices independently of protein tethering and porosity.”
Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks. (2016, background): “MSCs, for instance, adapt their differentiation profile to the local stiffness [64].”
A practical guide to hydrogels for cell culture (2016, background): “This has been exemplified by elegant studies that illustrate the influence of substrate stiffness on cell motility 62 , spreading 62,65 , and differentiation 65,66 .”