Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin
Abstract The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering differential mechanoresponses. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the ab...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Communications Materials |
| Online Access: | https://doi.org/10.1038/s43246-024-00444-0 |
| _version_ | 1797349789922230272 |
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| author | Nikhil Mittal Etienne B. Michels Andrew E. Massey Yunxiu Qiu Shaina P. Royer-Weeden Bryan R. Smith Alexander X. Cartagena-Rivera Sangyoon J. Han |
| author_facet | Nikhil Mittal Etienne B. Michels Andrew E. Massey Yunxiu Qiu Shaina P. Royer-Weeden Bryan R. Smith Alexander X. Cartagena-Rivera Sangyoon J. Han |
| author_sort | Nikhil Mittal |
| collection | DOAJ |
| description | Abstract The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering differential mechanoresponses. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has a stronger contribution than Arp2/3 to both traction and actin flow. Intriguingly, despite only slight changes in F-actin flow speed observed in cells with the combined inhibition of Arp2/3 and myosin compared to cells with sole myosin inhibition, they show a 4-times reduction in traction than cells with myosin-only inhibition. Our analyses indicate that traditional models based on rigid F-actin are inadequate for capturing such dramatic force reduction with similar actin flow. Instead, incorporating the F-actin network’s viscoelastic properties is crucial. Our new model including the F-actin viscoelasticity reveals that Arp2/3 and formin enhance stiffness sensitivity by mechanically reinforcing the F-actin network, thereby facilitating more effective transmission of flow-induced forces. This model is validated by cell stiffness measurement with atomic force microscopy and experimental observation of model-predicted stiffness-dependent actin flow fluctuation. |
| first_indexed | 2024-03-08T12:35:31Z |
| format | Article |
| id | doaj.art-879df1cdbaa4430cbba3ee0880941cc0 |
| institution | Directory Open Access Journal |
| issn | 2662-4443 |
| language | English |
| last_indexed | 2024-03-08T12:35:31Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Materials |
| spelling | doaj.art-879df1cdbaa4430cbba3ee0880941cc02024-01-21T12:28:06ZengNature PortfolioCommunications Materials2662-44432024-01-015111910.1038/s43246-024-00444-0Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actinNikhil Mittal0Etienne B. Michels1Andrew E. Massey2Yunxiu Qiu3Shaina P. Royer-Weeden4Bryan R. Smith5Alexander X. Cartagena-Rivera6Sangyoon J. Han7Department of Biomedical Engineering, Michigan Technological UniversityDepartment of Biomedical Engineering, Michigan Technological UniversitySection on Mechanobiology, National Institute of Biomedical Imaging and Bioengineering, National Institutes of HealthDepartment of Biomedical Engineering, Michigan State UniversityDepartment of Biomedical Engineering, Michigan Technological UniversityDepartment of Biomedical Engineering, Michigan State UniversitySection on Mechanobiology, National Institute of Biomedical Imaging and Bioengineering, National Institutes of HealthDepartment of Biomedical Engineering, Michigan Technological UniversityAbstract The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering differential mechanoresponses. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has a stronger contribution than Arp2/3 to both traction and actin flow. Intriguingly, despite only slight changes in F-actin flow speed observed in cells with the combined inhibition of Arp2/3 and myosin compared to cells with sole myosin inhibition, they show a 4-times reduction in traction than cells with myosin-only inhibition. Our analyses indicate that traditional models based on rigid F-actin are inadequate for capturing such dramatic force reduction with similar actin flow. Instead, incorporating the F-actin network’s viscoelastic properties is crucial. Our new model including the F-actin viscoelasticity reveals that Arp2/3 and formin enhance stiffness sensitivity by mechanically reinforcing the F-actin network, thereby facilitating more effective transmission of flow-induced forces. This model is validated by cell stiffness measurement with atomic force microscopy and experimental observation of model-predicted stiffness-dependent actin flow fluctuation.https://doi.org/10.1038/s43246-024-00444-0 |
| spellingShingle | Nikhil Mittal Etienne B. Michels Andrew E. Massey Yunxiu Qiu Shaina P. Royer-Weeden Bryan R. Smith Alexander X. Cartagena-Rivera Sangyoon J. Han Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin Communications Materials |
| title | Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin |
| title_full | Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin |
| title_fullStr | Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin |
| title_full_unstemmed | Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin |
| title_short | Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin |
| title_sort | myosin independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin |
| url | https://doi.org/10.1038/s43246-024-00444-0 |
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