%0 Journal Article %J Nat Mater %D 2016 %T Hydrogels with tunable stress relaxation regulate stem cell fate and activity %A Chaudhuri, Ovijit %A Gu, Luo %A Klumpers, Darinka %A Darnell, Max %A Bencherif, Sidi A %A Weaver, James C %A Huebsch, Nathaniel %A Lee, Hong-Pyo %A Lippens, Evi %A Duda, Georg N %A Mooney, David J %K Alginates %K Biomechanical Phenomena %K Cell Culture Techniques %K Cell Differentiation %K Extracellular Matrix %K Glucuronic Acid %K Hexuronic Acids %K Humans %K Hydrogels %K Mesenchymal Stromal Cells %K Stress, Mechanical %X Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel's initial elastic modulus, degradation, and cell-adhesion-ligand density. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture. %B Nat Mater %V 15 %P 326-34 %8 2016 Mar %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26618884?dopt=Abstract %R 10.1038/nmat4489