Dynamic molecular processes mediate cellular mechanotransduction
Open accessAbstract
Cellular responses to mechanical forces are crucial in embryonic development and adult physiology, and are involved in numerous diseases, including atherosclerosis, hypertension, osteoporosis, muscular dystrophy, myopathies and cancer. These responses are mediated by load-bearing subcellular structures, such as the plasma membrane, cell-adhesion complexes and the cytoskeleton. Recent work has demonstrated that these structures are dynamic, undergoing assembly, disassembly and movement, even when ostensibly stable. An emerging insight is that transduction of forces into biochemical signals occurs within the context of these processes. This framework helps to explain how forces of varying strengths or dynamic characteristics regulate distinct signalling pathways.
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For many cell types, cells sense substrate stiffness through integrin-mediated events involving focal adhesions, actin organization, and stress fiber development.
“It has been shown, for many cell types, that cells sense the stiffness of their substrata through integrin-mediated events involving focal adhesions, actin organization and development of stress fibers.55–57”
From Student award winner in the undergraduate category for the society of biomaterials 9th World Biomaterials Congress, Chengdu, China, June 1–5, 2012: The effects of substrate stiffness on the <i>in vitro</i> activation of macrophages and <i>in vivo</i> host response to poly(ethylene glycol)‐based hydrogels (2012) · cites this paper as [57]
The stiffer the substrate, the stronger the focal adhesions and the more organized the stress fibers.
“The overwhelming observations are that the stiffer the substrate, the stronger the focal adhesions are and the more organized the stress fibers are.”
From Student award winner in the undergraduate category for the society of biomaterials 9th World Biomaterials Congress, Chengdu, China, June 1–5, 2012: The effects of substrate stiffness on the <i>in vitro</i> activation of macrophages and <i>in vivo</i> host response to poly(ethylene glycol)‐based hydrogels (2012) · cites this paper as [57]
Cellular prestress development from these events is thought to trigger downstream events implicated in morphogenesis, physiology, and disease.
“It is thought that the development of cellular prestress as a result of these events trigger a wide range of downstream events in the cell that have been implicated in morphogensis, physiology and disease.57”
From Student award winner in the undergraduate category for the society of biomaterials 9th World Biomaterials Congress, Chengdu, China, June 1–5, 2012: The effects of substrate stiffness on the <i>in vitro</i> activation of macrophages and <i>in vivo</i> host response to poly(ethylene glycol)‐based hydrogels (2012) · cites this paper as [57]
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Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues
Baker, B. M., & Chen, C. S. (2012) · Journal of Cell Science · doi:10.1242/jcs.079509 · Cited by 1,760 · see citing works
Role of the extracellular matrix in regulating stem cell fate
Watt, F. M., & Huck, W. T. S. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3620 · Cited by 861 · see citing works
Collagen as a double-edged sword in tumor progression
Fang, M., Yuan, J., Peng, C., & Li, Y. (2014) · Tumor Biology · doi:10.1007/s13277-013-1511-7 · Cited by 580 · see citing works
Mechanoreciprocity in cell migration
van Helvert, S., Storm, C., & Friedl, P. (2018) · Nature Cell Biology · doi:10.1038/s41556-017-0012-0 · Cited by 587 · see citing works
Lampi, M. C., & Reinhart-King, C. A. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0475 · Cited by 551 · see citing works
Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic mechanotransduction
Huang, X., Yang, N., Fiore, V. F., Barker, T. H., Sun, Y., Morris, S. W., Ding, Q., Thannickal, V. J., & Zhou, Y. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0050oc · Cited by 530 · see citing works
Blakney, A. K., Swartzlander, M. D., & Bryant, S. J. (2012) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34104 · Cited by 470 · see citing works
Amani, H., Arzaghi, H., Bayandori, M., Dezfuli, A. S., Pazoki‐Toroudi, H., Shafiee, A., & Moradi, L. (2019) · Advanced Materials Interfaces · doi:10.1002/admi.201900572 · Cited by 436 · see citing works
Cyclic stretching of soft substrates induces spreading and growth
Cui, Y., Hameed, F. M., Yang, B., Lee, K., Pan, C. Q., Park, S., & Sheetz, M. (2015) · Nature Communications · doi:10.1038/ncomms7333 · Cited by 320 · see citing works
Cellular Mechanotransduction Relies on Tension-Induced and Chaperone-Assisted Autophagy
Ulbricht, A., Eppler, F. J., Tapia, V. E., van der Ven, P. F. M., Hampe, N., Hersch, N., Vakeel, P., Stadel, D., Haas, A., Saftig, P., et al. (2013) · Current Biology · doi:10.1016/j.cub.2013.01.064 · Cited by 288 · see citing works
Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix
Pakshir, P., Alizadehgiashi, M., Wong, B., Coelho, N. M., Chen, X., Gong, Z., Shenoy, V. B., McCulloch, C. A., & Hinz, B. (2019) · Nature Communications · doi:10.1038/s41467-019-09709-6 · Cited by 281 · see citing works
Van De Water, L., Varney, S., & Tomasek, J. J. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0393 · Cited by 251 · see citing works
Stretchable Electrochemical Sensors for Cell and Tissue Detection
Liu, Y., & Huang, W. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202007754 · Cited by 105 · see citing works
Bush, M., Alhanshali, B. M., Qian, S., Stanley, C. B., Heller, W. T., Matsui, T., Weiss, T. M., Nicholl, I. D., Walz, T., Callaway, D. J. E., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911489116 · Cited by 42 · see citing works
De Palma, S., Capitanio, D., Vasso, M., Braghetta, P., Scotton, C., Bonaldo, P., Lochmüller, H., Muntoni, F., Ferlini, A., & Gelfi, C. (2014) · Journal of Proteome Research · doi:10.1021/pr500675e · Cited by 40 · see citing works
Amado-Azevedo, J., Valent, E. T., & Van Nieuw Amerongen, G. P. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1828-6 · Cited by 36 · see citing works
- Authors
- Hoffman, B. D., Grashoff, C., & Schwartz, M. A.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Schwartz, Martin A.
- Venue
- Nature
- Published
- 2011-07-20
- Volume
- 475
- Issue
- 7356
- Pages
- 316-323
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6449687
- OpenAlex
- W1968409252
- Cited by
- 956
- References
- 95
- Citations by year
- 2026: 34 · 2025: 39 · 2024: 49 · 2023: 59 · 2022: 49 · 2021: 66 · 2020: 72 · 2019: 53 · 2018: 69 · 2017: 68 · 2016: 67 · 2015: 91 · 2014: 67 · 2013: 77 · 2012: 84
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- American Heart Association
- National Heart, Lung, and Blood Institute (R01HL075092)
- 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 › Cell Biology › Skin and Cellular Biology Research
- Keywords
- mechanotransduction, mechanical forces, cytoskeleton, cell adhesion complexes, plasma membrane, load-bearing structures
- MeSH terms
- Animals, Humans, Models, Biological, Subcellular Fractions, Mechanotransduction, Cellular, Biophysical Phenomena
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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