Synthetic fibrous hydrogels as a platform to decipher cell–matrix mechanical interactions
(2023) In Proceedings of the National Academy of Sciences of the United States of America 120(15).- Abstract
Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell–matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to... (More)
Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell–matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell–matrix interactions and to improve the design of materials for mechanobiology studies.
(Less)
- author
- organization
- publishing date
- 2023-04-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- biomaterials, cellular traction forces, cell–matrix interactions, mechanobiology, nonlinear mechanics
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 120
- issue
- 15
- article number
- e2216934120
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:37011188
- scopus:85151633256
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.2216934120
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: ACKNOWLEDGMENTS. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant (840290 and 642687), the National Natural Science Foundation of China (51803046 and 32201097), the High-Level Talents Foundation of Hebei Province (no. CG2020030001), the Excellent Young Scientist Fund of the Natural Science Foundation of Hebei Province (B2022202027), the Shenzhen Fundamental Research Foundation (JCYJ20210324115814040), and the Netherlands Ministry of Education, Culture and Science, Gravitation program grant no. 024.001.035. This work was also supported by the Research Foundation—Flanders (FWO, projects G0A5817N, G0D4519N, G0H6316N, I009718N, G087018N, G0C2422N, and 1529418N) and by KU Leuven (IDN/20/021, C14/16/053, C14/17/111, and KA/20/026). H.Y., M.C., J.B.-F., B.L, and J.V. acknowledge the support from the FWO for their fellowships (12A2423N, 12ZR120N, 1259223N, 11B1119N, and 1186220N). H.Y. and K.L. acknowledge the support for their EMBO short-term fellowships (8910 and 7424). Last but not least, we thank Prof. Changshun Ruan for his kind support on rheological measurements and valuable suggestions. Publisher Copyright: Copyright © 2023 the Author(s).
- id
- e94af2a0-62f7-4703-b786-794b1385c5a1
- date added to LUP
- 2024-01-12 14:01:54
- date last changed
- 2024-04-13 07:28:41
@article{e94af2a0-62f7-4703-b786-794b1385c5a1,
abstract = {{<p>Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell–matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell–matrix interactions and to improve the design of materials for mechanobiology studies.</p>}},
author = {{Yuan, Hongbo and Liu, Kaizheng and Cóndor, Mar and Barrasa-Fano, Jorge and Louis, Boris and Vandaele, Johannes and de Almeida, Paula and Coucke, Quinten and Chen, Wen and Oosterwijk, Egbert and Xing, Chengfen and Van Oosterwyck, Hans and Kouwer, Paul H.J. and Rocha, Susana}},
issn = {{0027-8424}},
keywords = {{biomaterials; cellular traction forces; cell–matrix interactions; mechanobiology; nonlinear mechanics}},
language = {{eng}},
month = {{04}},
number = {{15}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Synthetic fibrous hydrogels as a platform to decipher cell–matrix mechanical interactions}},
url = {{http://dx.doi.org/10.1073/pnas.2216934120}},
doi = {{10.1073/pnas.2216934120}},
volume = {{120}},
year = {{2023}},
}