2026-04-29T04:09:26Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/255372025-12-18T13:01:39Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Huerta-López, Carla author Clemente-Manteca, Alejandro author Velázquez-Carreras, Diana author Espinosa, Francisco M author Sanchez, Juan G author Martínez-Del-Pozo, Álvaro author García-García, María author Martín-Colomo, Sara author Rodríguez-Blanco, Andrea author Esteban-González, Ricardo author Martín-Zamora, Francisco M author Gutierrez-Rus, Luis I author Garcia, Ricardo author Roca-Cusachs, Pere author Elosegui-Artola, Alberto author Del Pozo, Miguel A author Herrero-Galán, Elías author Sáez, Pablo author Plaza, Gustavo R author Alegre-Cebollada, Jorge author Huerta-López, Carla author Clemente-Manteca, Alejandro author Velázquez-Carreras, Diana author Espinosa, Francisco M author Sanchez, Juan G author Martínez-Del-Pozo, Álvaro author García-García, María author Martín-Colomo, Sara author Rodríguez-Blanco, Andrea author Esteban-González, Ricardo author Martín-Zamora, Francisco M author Gutierrez-Rus, Luis I author Garcia, Ricardo author Roca-Cusachs, Pere author Elosegui-Artola, Alberto author Del Pozo, Miguel A author Herrero-Galán, Elías author Sáez, Pablo author Plaza, Gustavo R author Alegre-Cebollada, Jorge author 2024-11-15 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. Sci Adv. 2024 Nov 15;10(46):eadf9758. https://hdl.handle.net/20.500.12105/25537 39546608 SCIENCE ADVANCES Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing.