Hydrogels with tunable stress relaxation regulate stem cell fate and activity
By Ovijit Chaudhuri, Luo Gu, D. Klumpers, Max C Darnell, S. Bencherif, J. Weaver, Nathaniel Huebsch, Hong-pyo Lee, E. Lippens, G. Duda and 1 more. Nature Materials, 2015
2,105 citations recorded by the source corpus.
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, cell-adhesion-ligand density and degradation. 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.
Subfields: Biomedical Engineering, Cell Biology
View Paper: https://www.semanticscholar.org/paper/cdc09c981f33a5a8243b3f5f07c6ba33f63543b9
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Citations in the corpus
- Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores. (2017, positive): “At the mechanical level, YAP is regulated by mechanical cues such as extracellular matrix (ECM) rigidity, strain, shear stress, or adhesive area (Aragona et al., 2013; Benham-Pyle et al., 2015; Calvo et al., 2013; Chaudhuri et al., 2016; Dupont et al., 2011; Elosegui-Artola et al., 2016; Nakajima et”
- Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity (2021, background): “More interestingly, the fast relaxation rate of hydrogel scaffold matrix also promoted the spreading, proliferation and osteogenic differentiation potential of carried MSCs.(27) Under the same hydrogel scaffold system mentioned above, researchers found that MDA-MB231 breast cancer cells in high plas”
- Modeling Physiological Events in 2D vs. 3D Cell Culture. (2017, methodology): “(19) used alginate/collagen hydrogels as synthetic ECM to examine the effect of stress relaxation of the hydrogel on the cell spreading, proliferation, and differentiation of mesenchymal stem cells.”