Piezo1 regulates the mechanotransduction of soft matrix viscoelasticity
Mechanosensitive ion channels such as Piezo1 have fundamental roles in sensing the mechanical properties of the extracellular matrix. However, whether and how Piezo1 senses time-dependent matrix mechanical properties, that is, viscoelasticity, remains unknown. To address this question, we combine an immortalised mesenchymal stem cell line, in which Piezo1 expression can be silenced, with soft and stiff viscoelastic hydrogels that have independently tuneable elastic and viscous moduli. We demonstrate that Piezo1 is a regulator of the mechanotransduction of viscoelasticity in soft matrices, both experimentally and through simulations incorporating Piezo1 into a modified viscoelastic molecular clutch model. Using RNA sequencing, we also identify the transcriptomic responses of mesenchymal stem cells to matrix viscoelasticity and Piezo1 activity, identifying gene signatures that reflect their mechanobiology in soft and stiff viscoelastic hydrogels.
Authors
- Manuel Salmerón‐Sánchez (ORCID: https://orcid.org/0000-0002-8112-2100)
- Massimo Vassalli (ORCID: https://orcid.org/0000-0002-3063-4376)
- Paul G. Genever (ORCID: https://orcid.org/0000-0002-5730-8976)
- Pere Roca‐Cusachs (ORCID: https://orcid.org/0000-0001-6947-961X)
- Sirio Dupont (ORCID: https://orcid.org/0000-0002-6869-1966)
- Oana Dobre (ORCID: https://orcid.org/0000-0003-1968-5428)
- Giuseppe Ciccone (ORCID: https://orcid.org/0000-0002-7677-6257)
- Mariana Azevedo González Oliva (ORCID: https://orcid.org/0000-0002-3195-067X)
- Jiajun Luo (ORCID: https://orcid.org/0000-0003-4735-102X)
- Patrizia Romani (ORCID: https://orcid.org/0000-0002-1149-4304)
- Gotthold Fläschner
- Jonah L. Voigt (ORCID: https://orcid.org/0009-0009-7380-5524)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- University of Padua (IT)
- Institut Barcelona d'Estudis Internacionals (ES)
- Max Planck Institute for Medical Research (DE)
- Barcelona Institute of Science and Technology (ES)
- Institute for Bioengineering of Catalonia (ES)
- University of York (GB)
- University of Bayreuth (DE)
- University of Glasgow (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-15
- DOI
- https://doi.org/10.1038/s41467-025-64185-5
- Citations
- 7
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 8.15
Funders
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Institució Catalana de Recerca i Estudis Avançats
- Ministerio de Ciencia e Innovación
- Associazione Italiana per la Ricerca sul Cancro
- Engineering and Physical Sciences Research Council
- Agencia Estatal de Investigación