How you feel – explained

Images of Piezo1
Composite of a cryo-electron microscopy image showing lipid vesicles with embedded Piezo channels, and the Piezo channel structure (top). Topographic image of a single Piezo channel under force as recorded by high-speed atomic force microscopy (circle) and its lateral expansion in the membrane as a function of applied force (right). All images: Dr. Simon Scheuring.

The T.C. Team

Every time you pick up a call on your cellphone, you rely on the piezoelectric effect, which converts electricity into motion or the converse, in this case letting you hear your caller yodeling into your ear.

Thing is, the piezoelectric effect is not limited to the crystals and other materials used in electronics; it is ingrained in your very flesh. Piezo proteins make sense of touch work. It ensures your body knows when your blood pressure is high, your stomach is full, you are tilting to one side, or even hearing the sound of the air-conditioner.

While piezo proteins send an electrical signal under mechanical pressure, the first protein found that did that was called TREK, courtesy Frederick Sachs, a researcher at the State University of New York, Buffalo. Piezo proteins have been found even on the cell membranes of protozoa – single-celled creatures. But researchers have found at least two versions of it in vertebrates, and so very creatively named them Piezo1 and Piezo2.

'Triskelion' architecture of Piezo1
The three-bladed ‘triskelion’ architecture of Piezo1

They soon found out that Piezo1 looked a bit like a three-bladed fan – called a triskelion – with a pore at the center connecting the inside to the outside of the cell. From the side, Piezo1 looks a bit like a shallow bowl.

Now researchers from Weill Cornell Medicine and Rockefeller University – both institutions located conveniently next to each other – relied on cryo-electron and atomic force microscopy.

Cryo-electron microscopy also uses electrons to probe samples – much like the older electron microscopes. But the sample is frozen and a less powerful electron beam is used to reduce damage. The result is a far sharper image. Atomic force microscopy relies on fast-moving piezoelectric sensors to not only accurately form an image of the material being studied but also how deformable they are.

In the case of the Piezo1 they studied, they tested it on a smooth mica base. The result of combining these techniques were far sharper images and a better understanding of the fine structure of the protein.

Side view of Piezo1
Side view of Piezo1. Red line indicates structural changes when ion channel is open

The researchers found that pressure caused the springy blades of Piezo1 to compress and spread out, opening the pore and letting positively-charged calcium and other ions into the cell. Since Piezo2 has a similar structure, it may work in a similar fashion.

“As the membrane tension increases, the structure of Piezo1 flattens and stretches out to occupy a larger area, which in turn opens the ion channel,” co-senior author Simon Scheuring said, according to a press release. Scheuring is a professor of physiology and biophysics in anesthesiology at Weill Cornell Medicine. His team worked with the laboratory of Roderick MacKinnon, a professor of molecular neurobiology and biophysics at Rockefeller University. MacKinnon won the Nobel Prize in 2003 for his own work determining the structures and mechanisms of ion channel proteins. The first author was Yi-Chih Lin, a postdoctoral associate in anesthesiology.

Proposed mechanisms of action of Piezo1 in response to force.
Proposed mechanisms of action of Piezo1 in response to force. Left: Changes in membrane properties, such as tension or curvature, lead to a force that opens Piezo1. Right: Piezo1 channel is activated when structures inside or outside the cell push or pull on the ion channel

Scheuring said the shape of Piezo1 could let it be stretched and flattened by pulling forces on its ‘wings’ or forces on part of it that stuck out of the cell.

He said the information could help treat some diseases. As an example, Scheuring pointed out that excess cholesterol in the cell membranes of blood vessels could make the membranes stiffer, meaning that the embedded Piezo 1 would not bend as much. This could make them less likely to react to applied force and regulate blood pressure.

Details of the research were just published in Nature, so don’t hold your breath for your piezoelectric blood pressure governor. At least not quite yet.

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