Local nascent protein deposition and remodelling guide mesenchymal stromal cell mechanosensing and fate in three-dimensional hydrogels
Open accessAbstract
Hydrogels serve as valuable tools for studying cell-extracellular matrix interactions in three-dimensional environments that recapitulate aspects of native extracellular matrix. However, the impact of early protein deposition on cell behaviour within hydrogels has largely been overlooked. Using a bio-orthogonal labelling technique, we visualized nascent proteins within a day of culture across a range of hydrogels. In two engineered hydrogels of interest in three-dimensional mechanobiology studies-proteolytically degradable covalently crosslinked hyaluronic acid and dynamic viscoelastic hyaluronic acid hydrogels-mesenchymal stromal cell spreading, YAP/TAZ nuclear translocation and osteogenic differentiation were observed with culture. However, inhibition of cellular adhesion to nascent proteins or reduction in nascent protein remodelling reduced mesenchymal stromal cell spreading and nuclear translocation of YAP/TAZ, resulting in a shift towards adipogenic differentiation. Our findings emphasize the role of nascent proteins in the cellular perception of engineered materials and have implications for in vitro cell signalling studies and application to tissue repair.
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The viscous properties of the shear-thinning hydrogel allow cells to remodel their surrounding environment in protease-independent mechanisms with local hydrogel yielding at the spheroid-hydrogel interface, which is reduced in more elastic networks.
“The viscous properties of the shear-thinning hydrogel investigated here allows cells to remodel their surrounding environment in protease-independent mechanisms with local hydrogel yielding at the spheroid-hydrogel interface39, which is reduced in more elastic networks.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [39]
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- Authors
- Loebel, C., Mauck, R. L., & Burdick, J. A.
- Affiliations
- Philadelphia VA Medical Center (US)
- University of Pennsylvania (US)
- Corresponding author
- Burdick, Jason A.
- Venue
- Nature Materials
- Published
- 2019-03-18
- Volume
- 18
- Issue
- 8
- Pages
- 883-891
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- PMC
- PMC6650309
- OpenAlex
- W2920808209
- Cited by
- 402
- References
- 65
- Citations by year
- 2026: 33 · 2025: 56 · 2024: 50 · 2023: 47 · 2022: 60 · 2021: 77 · 2020: 61 · 2019: 18
- FWCI
- 18.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institute of Biomedical Imaging and Bioengineering (R01EB008722)
- 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
- extracellular matrix remodeling, mesenchymal stem cells, mechanosensing, three-dimensional hydrogels, hyaluronic acid hydrogel, osteogenic differentiation, adipogenesis, cell spreading, cell adhesion, biodegradable hydrogels, viscoelastic hydrogels, mechanobiology
- MeSH terms
- Cell Adhesion, Humans, Proteins, Signal Transduction, Cell Lineage, Hydrogels, Mechanotransduction, Cellular, Mesenchymal Stem Cells
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