Before 2010, scientists knew very little about how the sensation of touch begins its journey into a person’s consciousness. They knew that nerve endings help carry the message from different parts of our bodies to our brains. But they didn’t know what kind of receptor on the nerve ending causes the message to fire — for example, when a person touches an ice cube or places a hand on a hot stove. You could say that researchers understood the wires, but not the light switch.
Then came Ardem Patapoutian.
In 2010, Patapoutian and his colleagues at the Scripps Research Institute discovered the proteins that serve as two kinds of switches — proteins called Piezo1 and Piezo2 (piezo is Greek for the verb “to press”). This week, Patapoutian shared a Nobel prize with David Julius, who similarly discovered how sensations of heat and cold enter our awareness.
In mammals like humans, piezo receptors transmit mechanical sensations to the nervous system. When cells that contain these piezo receptors are stretched, the receptors open up, letting in ions (charged particles) and setting off an electrical pulse.
But each type of receptor has a slightly different use. Piezo1 is part of our body’s built-in blood pressure monitoring system, as well as other internal systems that rely on pressure-sensing. Piezo2, on the other hand, is “the principle mechanosensor for touch and proprioception,” Patapoutian told me in 2019.
That is, without Piezo2, we couldn’t feel another person’s hand graze our own.
Proprioception, which also relies on Piezo2, is less well-known than the sense of touch, but it’s sometimes referred to as the body’s “sixth” sense. It’s our sense of where our bodies are in three-dimensional space.
It’s easier to explain proprioception with a demonstration. If you put a cup out in front of you and then close your eyes, you can still find the cup with your hand. Proprioception is what guides your intuition of how far to move your hand and in which direction.
“It’s truly fascinating that we are not aware of it,” Patapoutian said of proprioception during a 2019 interview with Vox. “When I give lectures, even to college students or graduate students, I sometimes ask: “How many people know of proprioception?” Even specialized biologists often don’t know anything about it.”
I spoke to Patapoutian for a story about people who are missing Piezo2 receptors in their bodies because of a genetic inheritance. When they close their eyes, “it’s like I am lost,” one of them told me. With their eyes closed, they cannot reach for the cup in front of them. They have no idea where it is. They have no idea where their arms are in space.
Patapoutian helped me understand that the human sense of touch contains multitudes — and to this day, scientists don’t fully understand it. But as scientists learn more about touch receptors, they’re also figuring out how to tend to a body that’s in pain.
This conversation, which took place in 2019, has been edited for length and clarity.
Brian Resnick
What is the sense of touch?
Ardem Patapoutian
We think about the five senses: vision, olfaction, taste, hearing, and touch. If you really start digging deep into touch, it’s so different than the rest of the senses.
When you talk about touch, there’s so many modalities to it: There’s different physical forces we sense, like temperature and mechanical force. There’s itch. There’s this [spectrum] of pleasant touch to noxious to painful.
It’s a very complex system. The demarcation of when pleasant touch ends and painful touch starts is actually very flexible. If you have a sunburn, for example, the same amount of touch that could have been pleasant becomes painful.
All of what I was just talking about is sensation on skin.
Again, if you put on top of it proprioception and internal organ sensation, it’s a very complicated sense that we don’t really understand. There’s no totally, well-agreed terminology even to describe clearly what we mean by touch and somatosensation.
Brian Resnick
How is proprioception related to touch?
Ardem Patapoutian
Proprioception is dependent on your sensory system detecting muscle stretch. When that muscle gets stretched, these nerve endings that are wrapped around it can sense it. Piezo2 is actually sitting right at the ends of these nerves, where [they] wrap around the muscle.
When you close your eyes and touch your nose, how are you doing this? What’s the information that you’re basing this on? It’s all about learning, as you grow up, to sense how much each of these muscles are being stretched when you’re making these complex motions of your hand. From that, you know exactly where things are.
People sometimes call it muscle memory. It’s actually mostly these proprioceptive neurons that are giving you this understanding of where your limbs are compared to your body — simply from detecting how much your tendons and muscles are being stretched.
Brian Resnick
Touch and proprioception use the same receptor: Piezo2. But all those other sensations you described — temperature, itch, pain — do those all enter us through different receptors? Is it the case that all these different types of touch feelings have a different specific molecule responsible for them?
Ardem Patapoutian
Absolutely, the molecules are different. There are temperature sensors at very different ranges of temperature. Cold, heat, warm are all different.
From 2000 to 2010, my lab studied temperature sensation. We, for example, identified the first cold-activated ion channel. It ended up also being the receptor for menthol. Anytime you use one of these chewing gums or toothpastes that gives that cooling sensation in your mouth, it hijacks the cold-activated channel.
Brian Resnick
Is the goal to try to find the sensor responsible for each sensation?
Ardem Patapoutian
Yeah. What seems to have worked is starting with a very reductionist approach, in the sense of finding the sensor.
Brian Resnick
Are some of these sensors still elusive?
Ardem Patapoutian
Absolutely. Without Piezo2, you don’t have touch, you don’t have proprioception. However, acute touch — the hammer hitting your finger “ouch” kind of feeling — the identity of these ion channels that account for acute pain is still unknown.
Brian Resnick
I don’t know if this gets more into philosophy than science, but are we just the sum of all these inputs?
Ardem Patapoutian
I think the clear thing one has to realize is that sensory biology is not telling us about reality. It is representing reality.
[Reality is] very related to these senses. But that’s the thing I would emphasize — it’s kind of an approximation. We’re interpreting the world according to what sensory systems we have.