Hydrogels with tunable stress relaxation regulate stem cell fate and activity
Open accessAbstract
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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The viscoelastic properties of a material affect matrix remodeling, cell spreading, migration, differentiation, and consequently, organoid fate.
“The viscoelastic properties of a material affect matrix remodeling, cell spreading, migration, differentiation, and consequently, organoid fate139–141.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [139]
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- Authors
- 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.
- Affiliations
- Harvard University (US)
- Gladstone Institutes (US)
- Stanford University (US)
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- Corresponding author
- Mooney, David J.
- ORCID
- Venue
- Nature Materials
- Published
- 2015-11-30
- Volume
- 15
- Issue
- 3
- Pages
- 326-334
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- PMC
- PMC4767627
- OpenAlex
- W2270498673
- Cited by
- 2,443
- References
- 51
- Citations by year
- 2026: 290 · 2025: 284 · 2024: 258 · 2023: 257 · 2022: 256 · 2021: 275 · 2020: 249 · 2019: 206 · 2018: 175 · 2017: 126 · 2016: 65
- FWCI
- 50.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- ZonMw (918.11.635)
- Einstein Stiftung Berlin
- Berlin-Brandenburger Centrum für Regenerative Therapien
- Berlin-Brandenburg School for Regenerative Therapies (GSC203)
- National Institutes of Health (DMR-1420570)
- Materials Research Science and Engineering Center, Harvard University (DMR- 1420570, 1420570)
- National Cancer Institute (CA153802, F32CA153802)
- National Institute of Dental and Craniofacial Research (R01DE013033)
- Division of Materials Research (DMR 14–20570, 1420570)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- hydrogels, stress relaxation, mesenchymal stem cells, osteogenic differentiation, extracellular matrix mechanics, viscoelasticity, 3D cell culture, cell adhesion, actomyosin contractility, biomaterial design, cell-matrix interactions
- MeSH terms
- Alginates, Biomechanical Phenomena, Cell Differentiation, Extracellular Matrix, Hexuronic Acids, Humans, Stress, Mechanical, Cell Culture Techniques, Hydrogels, Glucuronic Acid, Mesenchymal Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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