Tissue Cells Feel and Respond to the Stiffness of Their Substrate
Abstract
Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.
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Substrate stiffness affects bioactivities ranging from migration to differentiation.
“The microenvironment of cells is not only affected by microtopography but also by the stiffness of the substrate that cells adhere to, which affects bioactivities ranging from migration to differentiation (28).”
From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [28]
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- Authors
- Discher, D. E., Janmey, P., & Wang, Y.-L.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Discher, Dennis E.
- Venue
- Science
- Published
- 2005-11-18
- Volume
- 310
- Issue
- 5751
- Pages
- 1139-1143
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2054635074
- Cited by
- 6,382
- References
- 82
- Citations by year
- 2026: 287 · 2025: 269 · 2024: 239 · 2023: 237 · 2022: 318 · 2021: 269 · 2020: 369 · 2019: 389 · 2018: 399 · 2017: 432 · 2016: 379 · 2015: 392 · 2014: 407 · 2013: 369 · 2012: 380
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- substrate stiffness, mechanotransduction, cell-matrix adhesion, cell-substrate adhesion, soft agar, cancer cell detection, fibroblasts, muscle cells, neurons, actomyosin cytoskeleton, adhesion complexes, cell contractility, tissue stiffness, cell differentiation, tissue regeneration
- MeSH terms
- Biomechanical Phenomena, Cell Adhesion, Cell Communication, Cell Physiological Phenomena, Cytoskeleton, Elasticity, Humans, Muscle Contraction, Organogenesis
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