Hydrogels with tunable stress relaxation regulate stem cell fate and activity

O. Chaudhuri, L. Gu, D. Klumpers, M. Darnell, S.A. Bencherif, J.C. Weaver, N. Huebsch, H. P. Lee, E. Lippens, G. N. Duda, D.J. Mooney

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)326-334
JournalNat. Mater.
Volume15
DOIs
Publication statusPublished - 2016

Cite this

Chaudhuri, O., Gu, L., Klumpers, D., Darnell, M., Bencherif, S. A., Weaver, J. C., ... Mooney, D. J. (2016). Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater., 15, 326-334. https://doi.org/10.1038/nmat4489
Chaudhuri, O. ; Gu, L. ; Klumpers, D. ; Darnell, M. ; Bencherif, S.A. ; Weaver, J.C. ; Huebsch, N. ; Lee, H. P. ; Lippens, E. ; Duda, G. N. ; Mooney, D.J. / Hydrogels with tunable stress relaxation regulate stem cell fate and activity. In: Nat. Mater. 2016 ; Vol. 15. pp. 326-334.
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abstract = "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.",
author = "O. Chaudhuri and L. Gu and D. Klumpers and M. Darnell and S.A. Bencherif and J.C. Weaver and N. Huebsch and Lee, {H. P.} and E. Lippens and Duda, {G. N.} and D.J. Mooney",
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Chaudhuri, O, Gu, L, Klumpers, D, Darnell, M, Bencherif, SA, Weaver, JC, Huebsch, N, Lee, HP, Lippens, E, Duda, GN & Mooney, DJ 2016, 'Hydrogels with tunable stress relaxation regulate stem cell fate and activity' Nat. Mater., vol. 15, pp. 326-334. https://doi.org/10.1038/nmat4489

Hydrogels with tunable stress relaxation regulate stem cell fate and activity. / Chaudhuri, O.; Gu, L.; Klumpers, D.; Darnell, M.; Bencherif, S.A.; Weaver, J.C.; Huebsch, N.; Lee, H. P.; Lippens, E.; Duda, G. N.; Mooney, D.J.

In: Nat. Mater., Vol. 15, 2016, p. 326-334.

Research output: Contribution to journalArticleAcademicpeer-review

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AB - 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.

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Chaudhuri O, Gu L, Klumpers D, Darnell M, Bencherif SA, Weaver JC et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater. 2016;15:326-334. https://doi.org/10.1038/nmat4489