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<p>Mechanosensitive ion channels translate physical forces into biochemical signals, enabling cells to sense pressure, tension and tissue deformation. Piezo1, a trimeric mechanogated ion channel, is essential in processes such as vascular regulation and immune function, yet the force required for its activation has remained unclear because existing approaches couple applied force with membrane deformation, preventing direct calibration. Here we present a DNA-tethered extracellular force sensing platform that delivers calibrated piconewton forces directly to Piezo1 while simultaneously monitoring channel activity via a genetically encoded calcium reporter. Combining micropipette manipulation and DNA hairpin-based force calibration, we show that Piezo1 opens approximately at 15.0 pN, providing a direct quantification of its activation threshold and demonstrating that Piezo1 can be gated by tether-mediated forces independent of membrane tension, supporting a force from filament mechanism. This approach offers a generalizable strategy for precisely probing mechanotransduction pathways at the localized molecular sites and can be extended to diverse force responsive systems across biology and materials science.</p>

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Direct quantification of Piezo1 activation threshold through DNA-tethered extracellular force sensing

  • 期刊论文

  • 发表日期：

    2026年4月3日

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  • Mingyu Sui,
  • Jingzhun Liu,
  • Chaoyu Fu,
  • Yuxia Liu,
  • Jie Yan,
  • Xiaogang Liu

摘要

Mechanosensitive ion channels translate physical forces into biochemical signals, enabling cells to sense pressure, tension and tissue deformation. Piezo1, a trimeric mechanogated ion channel, is essential in processes such as vascular regulation and immune function, yet the force required for its activation has remained unclear because existing approaches couple applied force with membrane deformation, preventing direct calibration. Here we present a DNA-tethered extracellular force sensing platform that delivers calibrated piconewton forces directly to Piezo1 while simultaneously monitoring channel activity via a genetically encoded calcium reporter. Combining micropipette manipulation and DNA hairpin-based force calibration, we show that Piezo1 opens approximately at 15.0 pN, providing a direct quantification of its activation threshold and demonstrating that Piezo1 can be gated by tether-mediated forces independent of membrane tension, supporting a force from filament mechanism. This approach offers a generalizable strategy for precisely probing mechanotransduction pathways at the localized molecular sites and can be extended to diverse force responsive systems across biology and materials science.