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<p>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.</p>

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Piezo1 regulates the mechanotransduction of soft matrix viscoelasticity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月15日

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  • 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,
  • Manuel Salmeron-Sanchez

摘要

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.