Researchers at the National University of Singapore (NUS) have built a molecular "leash" to pull directly on a force-sensing protein called Piezo1, and discovered it switches on at about 15 piconewtons, proving that it can be activated by physical tethers, not only by membrane deformation.
The team developed a new method to directly measure how tiny mechanical forces activate a key protein in our cells, known as Piezo1, a sensor that allows cells to “feel” physical forces. Using a DNA-based approach, the team was able to apply extremely small, well-controlled forces on the order of trillionths of a newton to individual Piezo1 channels. At the same time, they monitored the channel’s activity in real time using a fluorescent signal that lights up when calcium ions enter the cell. Their key finding: Piezo1 can be switched on by a force of about 15 piconewtons, providing the first precise measurement of the force needed to activate this important sensor.
Why this matters
Cells constantly experience physical forces, from blood flow and touch to tissue movement. Proteins like Piezo1 help cells detect and respond to these forces, playing roles in processes such as blood pressure regulation, immune responses, and tissue repair and development. However, until now, scientists could not directly measure the amount of force required to activate Piezo1, because existing techniques also changed the shape of the cell membrane, making results difficult to interpret.
A new way to apply force using DNA
The NUS team, led by Professor Liu Xiaogang from the Department of Chemistry , NUS and Professor Yan Jie from the Department of Physics , NUS solved this problem by attaching Piezo1 to tiny beads using strands of DNA. This setup enabled the researchers to apply precise, well-calibrated forces directly to the protein while avoiding unwanted effects from membrane stretching. It also allowed them to measure the protein’s response at the single-molecule level.
The research breakthrough was published in the journal Nature Sensors .
A shift in understanding
Previously, scientists believed Piezo1 mainly responds to forces acting through the cell membrane. This study shows that forces transmitted through structures like the extracellular matrix or cytoskeleton can also directly activate the channel. This provides strong evidence for an alternative mechanism, sometimes described as “force-from-filament”, and suggests that cells may sense mechanical signals in more ways than previously thought.
Using this highly precise and flexible DNA-based system, the researchers showed that Piezo1 can be activated in a controlled, repeatable, and reversible way by applying defined forces. The platform offers exceptional spatial control, allowing scientists to study the response of individual ion channels to mechanical forces with high accuracy. Importantly, this method is not limited to Piezo1, as it can be adapted to investigate other force-sensitive proteins, offering a versatile tool to better understand how mechanical forces influence biological processes.
Dr Sui Mingyu, who is part of the research team said, “This work represents both a fundamental and technological advance in mechanobiology. By establishing a clear and quantitative link between applied force and ion channel activation while separating this effect from changes in the cell membrane, this approach opens up new ways to study the response of cells to physical forces in both health and disease.”
Looking ahead
In the future, this platform could help uncover force-dependent signaling pathways, support the development of new mechanosensitive therapies, and enable the design of materials that respond to mechanical stimuli.
Nature
Experimental study
Cells
Direct quantification of Piezo1 activation threshold through DNA-tethered extracellular force sensing
3-Apr-2026