Something as seemingly innocuous as a gentle tap on the skin signals specialized nerve cells to convert the physical force into an electrical signal to the brain. With a new study from scientists at Scripps Research in La Jolla, how that works has become clearer.
Senior co-author Ardem Patapoutian, a molecular biologist and neuroscientist at Scripps and a Howard Hughes Medical Institute investigator, helped discover a pair of “protein gates,” PIEZO1 and PIEZO2, that open in response to force. For his efforts, he shared the Nobel Prize in physiology or medicine with physicist and biochemist David Julius in 2021.
Though the gates appear similar, they are different. PIEZO1 responds to broad mechanical stresses such as cellular stretching across the body, while PIEZO2 is a key sensor for touch.
The study’s explanation of how PIEZO2 detects certain types of force and why it became the body’s main light-touch sensor was published March 4 in the scientific journal Nature.
The Scripps Research team used minimal fluorescence photon flux super-resolution microscopy to explore the difference between the two proteins.
Previous imaging techniques allowed for detailed but stationary images of frozen PIEZO proteins. MINFLUX, on the other hand, enables scientists to track proteins’ movements and positions with nanometer-scale precision, or 100,000 times smaller than the width of a human hair.
Eric Mulhall, a postdoctoral fellow in Patapoutian’s lab and the study’s co-senior author, described MINFLUX as “light microscopy on steroids.”
“The resolving power of this microscope is similar to being able to look up at the moon and see Neil Armstrong’s fingernail,” Mulhall said. “It’s incredible that we can basically look at molecules with microscopy.”
Patapoutian said in a statement that “what I love about this work, led by Eric Mulhall, is that it connects discoveries across an unusually wide range of scales. It’s one of the few studies I’ve seen that spans from nanometer-scale super-resolution microscopy all the way to ex vivo [outside the body] and in vivo [inside the body] experiments, linking single-molecule insights to physiological function.”
Scientists observed how PIEZO2 changed shape when force was introduced. Additional electrical recordings tracking ion flow, led by second author and staff scientist Oleg Yarishkin, showed a connection between structural changes in PIEZO2 and activity within the ion channel.
The team also found that PIEZO2 is stiffer than PIEZO1 and is tethered to a cell’s internal scaffolding, or cytoskeleton, which maintains the shape of the cell and transmits forces.
Mulhall said a stronger understanding of how people sense mechanical force can allow scientists to better understand what goes wrong in sensory disorders.
“In contrast with the other classic senses like vision, hearing, olfaction and taste … how we sense mechanical force in our somatosensory nervous system remains far less understood at a molecular level,” he said.
“I think this is particularly astonishing because our bodies have dedicated over 80% of our peripheral sensory nervous system to detecting mechanical force. So not knowing how it works at a molecular level … is pretty crazy.”
Read the full study at nature.com/articles/s41586-026-10182-7. ♦