DNA Leash Pins Piezo1 Activation at 15 Piconewtons
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- NUS researchers built a DNA-tethered molecular 'leash' to pull directly on Piezo1 and measured its activation threshold at approximately 15 piconewtons, the first precise quantification of the force required to open the channel.
- The new platform attaches Piezo1 to tiny beads via DNA strands, applying calibrated trillionths-of-a-newton forces to single channels while avoiding the membrane-stretching artifacts that confounded prior measurements.
- The findings challenge the prevailing model that Piezo1 responds mainly to membrane deformation, providing direct evidence for an alternative 'force-from-filament' mechanism in which cytoskeletal or extracellular-matrix tethers can open the channel.
- The setup monitors channel activity in real time via fluorescent calcium signals and produces controlled, repeatable, and reversible activation, with the team noting the method can be adapted to study other force-sensitive proteins beyond Piezo1.
- The study was led by Professor Liu Xiaogang (NUS Department of Chemistry) and Professor Yan Jie (NUS Department of Physics), with first author Dr. Sui Mingyu, and was published in the journal Nature Sensors (2026).
- Dr. Sui Mingyu said the work 'represents both a fundamental and technological advance in mechanobiology' by establishing a clear, quantitative link between applied force and ion channel activation independent of membrane changes.
Why it matters: Every prior tool for probing Piezo1 also bent the cell membrane, making it impossible to isolate tether-based activation. This DNA platform decouples those variables and yields a concrete 15-piconewton threshold that researchers can target when studying blood-pressure regulation, immune response, and tissue repair. The platform is generalizable to other mechanosensitive proteins.
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