Cyclic stretching of soft substrates induces spreading and growth
Open accessAbstract
In the body, soft tissues often undergo cycles of stretching and relaxation that may affect cell behaviour without changing matrix rigidity. To determine whether transient forces can substitute for a rigid matrix, we stretched soft pillar arrays. Surprisingly, 1–5% cyclic stretching over a frequency range of 0.01–10 Hz caused spreading and stress fibre formation (optimum 0.1 Hz) that persisted after 4 h of stretching. Similarly, stretching increased cell growth rates on soft pillars comparative to rigid substrates. Of possible factors linked to fibroblast growth, MRTF-A (myocardin-related transcription factor-A) moved to the nucleus in 2 h of cyclic stretching and reversed on cessation; but YAP (Yes-associated protein) moved much later. Knockdown of either MRTF-A or YAP blocked stretch-dependent growth. Thus, we suggest that the repeated pulling from a soft matrix can substitute for a stiff matrix in stimulating spreading, stress fibre formation and growth.
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In vitro studies have shown that fibroblast stretching can activate SRF-driven transcription and YAP1-TEAD-driven transcription.
“In vitro studies have shown that fibroblast stretching, which may result from the hyperproliferation of transformed epithelial cells, can activate SRF-driven transcription and Yes-associated protein 1 (YAP1)–TEAD-driven transcription53,54,65,66.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [66]
The Results and Discussion section (page not supplied) reports that cyclic stretching of fibroblasts on soft substrates caused MRTF-A and YAP to accumulate in the nucleus, and that depletion of either inhibited stretch-induced spreading. It does not show that stretching activated SRF-driven or YAP1–TEAD-driven transcription; nuclear accumulation is not a direct measurement of either transcriptional response. (LLM, conf=0.85)
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- Authors
- Cui, Y., Hameed, F. M., Yang, B., Lee, K., Pan, C. Q., Park, S., & Sheetz, M.
- Affiliations
- National University of Singapore (SG)
- Corresponding author
- Park, Sungsu
- Sheetz, Michael
- Venue
- Nature Communications
- Published
- 2015-02-23
- Volume
- 6
- Issue
- 1
- Pages
- 6333-6333
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4346610
- OpenAlex
- W2049233086
- Cited by
- 320
- References
- 33
- Citations by year
- 2026: 23 · 2025: 23 · 2024: 23 · 2023: 24 · 2022: 28 · 2021: 44 · 2020: 40 · 2019: 30 · 2018: 27 · 2017: 20 · 2016: 25 · 2015: 13
- FWCI
- 15.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Research Foundation
- National University of Singapore
- National Research Foundation Singapore
- Hanyang University
- Ministry of Science, ICT and Future Planning
- Mechanobiology Institute, Singapore
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Physical Sciences › Engineering › Biomedical Engineering › Elasticity and Material Modeling
- Keywords
- cyclic strain, soft substrates, cell spreading, cell growth, MRTF-A, YAP, mechanotransduction, fibroblasts, extracellular matrix stiffness
- MeSH terms
- Animals, Cells, Cultured, Fibroblasts, Stress, Mechanical, Cell Culture Techniques, Cell Shape, Cell Growth Processes, Mice
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