Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing
The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate...
| Autores: | , , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Recursos: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/420796 |
| Acesso em linha: | https://hdl.handle.net/2117/420796 https://dx.doi.org/10.1126/sciadv.adf9758 |
| Access Level: | acceso abierto |
| Palavra-chave: | Numerical analysis--Simulation methods Biomathematics Anàlisi numèrica Biomatemàtica Classificació AMS::65 Numerical analysis::65C Probabilistic methods, simulation and stochastic differential equations Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general Àrees temàtiques de la UPC::Matemàtiques i estadística::Anàlisi numèrica Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències |
| Resumo: | The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime. Here, we have exploited engineered stiff viscoelastic protein hydrogels to show that, contrary to current models of cell-ECM interaction, substrate viscous energy dissipation attenuates mechanosensing even when cells are exposed to higher effective rigidity. This unexpected behavior is however readily captured by a pull-and-hold model of molecular clutch–based cell mechanosensing, which also recapitulates opposite cellular response at low rigidities. Consistent with predictions of the pull-and-hold model, we find that myosin inhibition can boost mechanosensing on cells cultured on dissipative matrices. Together, our work provides general mechanistic understanding on how cells respond to the viscoelastic properties of the ECM. |
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