Piezo1 regulates the mechanotransduction of soft matrix viscoelasticity

Mariana A. G. Oliva, Giuseppe Ciccone, Gotthold Fläschner, Jiajun Luo, Jonah L. Voigt, Patrizia Romani, Paul Genever, Oana Dobre, Sirio Dupont, Massimo Vassalli, Pere Roca-Cusachs () and Manuel Salmeron-Sanchez ()
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Mariana A. G. Oliva: University of Glasgow
Giuseppe Ciccone: University of Glasgow
Gotthold Fläschner: The Barcelona Institute for Science and Technology (BIST)
Jiajun Luo: University of Glasgow
Jonah L. Voigt: University of Glasgow
Patrizia Romani: University of Padua
Paul Genever: University of York
Oana Dobre: University of Glasgow
Sirio Dupont: University of Padua
Massimo Vassalli: University of Glasgow
Pere Roca-Cusachs: The Barcelona Institute for Science and Technology (BIST)
Manuel Salmeron-Sanchez: University of Glasgow

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-64185-5

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