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Effects of extracellular matrix viscoelasticity on cellular behaviour
Open accessAbstract
Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins are widely used to assess the role of stiffness, and results from such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and ECMs are not linearly elastic materials-they exhibit far more complex mechanical behaviours, including viscoelasticity (a time-dependent response to loading or deformation), as well as mechanical plasticity and nonlinear elasticity. Here we review the complex mechanical behaviours of tissues and ECMs, discuss the effect of ECM viscoelasticity on cells, and describe the potential use of viscoelastic biomaterials in regenerative medicine. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and can promote behaviours that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments. These findings have provided insights into cell-matrix interactions and how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results suggest design guidelines for the next generation of biomaterials, with the goal of matching tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.
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“Therefore, other matrices with defined compositions64 have been explored as alternative matrices to Matrigel, such as recombinant human collagen62, fibrin65, or synthetic hydrogels3,63.”
From Organoids (2022) · cites this paper as [65]
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“Biological tissues are viscoelastic, which means that their mechanical behavior can be described as that of both a solid (elastic) and a liquid (viscous) [21,22,23].”
From Fascia Mobility, Proprioception, and Myofascial Pain. (2021) · cites this paper as [22]
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“dECM hydrogels are biomaterials that predominantly rely on the self-assembly process of collagen fibers, which can be regulated by glycosaminoglycans and other ECM proteins.”
From Constructing biomimetic microenvironments for liver regeneration (2025) · cites this paper as [159]
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“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 [140]
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Metadata
- Authors
- Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J., & Shenoy, V. B.
- Affiliations
- Stanford University (US)
- The University of Queensland (AU)
- University of Pennsylvania (US)
- Harvard University (US)
- Corresponding author
- Chaudhuri, Ovijit
- Cooper-White, Justin
- Janmey, Paul A.
- Mooney, David J.
- Shenoy, Vivek B.
- Venue
- Nature
- Published
- 2020-08-26
- Volume
- 584
- Issue
- 7822
- Pages
- 535-546
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7676152
- OpenAlex
- W3080362910
- Cited by
- 2,224
- References
- 205
- Citations by year
- 2026: 356 · 2025: 494 · 2024: 423 · 2023: 376 · 2022: 324 · 2021: 236 · 2020: 11
- FWCI
- 27.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (EB017753)
- National Cancer Institute (U54CA193417, U01CA214369, R01CA232256, R37CA214136, U01CA202177)
- National Institute of General Medical Sciences (R35GM136259)
- National Institute of Biomedical Imaging and Bioengineering (R01EB017753)
- National Institute of Dental and Craniofacial Research (R01DE013033)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- extracellular matrix stiffness, cell-matrix interactions, polyacrylamide hydrogel, PDMS elastomer, nonlinear elasticity, cell migration, cell proliferation, cell differentiation, organoid formation, regenerative medicine, in vitro tissue models, 3D cell culture
- MeSH terms
- Biocompatible Materials, Elasticity, Extracellular Matrix, Humans, Models, Biological, Cell Culture Techniques, Mechanotransduction, Cellular, Regenerative Medicine, Cell Shape, Viscoelastic Substances, Mesenchymal Stem Cells
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