Abstract
Mechanical force is an essential physical element that contributes to the formation and function of life. The discovery of the evolutionarily conserved PIEZO family, including PIEZO1 and PIEZO2 in mammals, as bona fide mechanically activated cation channels has transformed our understanding of how mechanical forces are sensed and transduced into biological activities. In this Review, I discuss recent structure–function studies that have illustrated how PIEZO1 and PIEZO2 adopt their unique structural design and curvature-based gating dynamics, enabling their function as dedicated mechanotransduction channels with high mechanosensitivity and selective cation conductivity. I also discuss our current understanding of the physiological and pathophysiological roles mediated by PIEZO channels, including PIEZO1-dependent regulation of development and functional homeostasis and PIEZO2-dominated mechanosensation of touch, tactile pain, proprioception and interoception of mechanical states of internal organs. Despite the remarkable progress in PIEZO research, this Review also highlights outstanding questions in the field.
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Acknowledgements
Owing to finding more than 1,000 papers from the PubMed search for PIEZO channels and the space limitation of this article, the author apologizes for not being able to include all of the reported literature. The author thanks W. Liu and T. Ye for help with figure preparation. This work was supported by grant numbers 2021ZD0203301, 32425003, 32130049, 32021002 and 31825014 to B.X. from the National Natural Science Foundation of China or the National Key R&D Program of China, the New Cornerstone Investigator Program, the Research Fund of Vanke School of Public Health and the Tsinghua University Initiative Scientific Research Program.
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Glossary
- Baroreceptor neurons
-
A specialized type of mechanoreceptor cells that detect changes in blood pressure.
- Force-from-filament (FFF) model
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(Also known as the tether model). A model proposing that an ion channel is physically tethered to the extracellular matrix or intracellular accessory structures such as the cytoskeleton, affecting its mechanogating properties.
- Force-from-lipids (FFL) model
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A model proposing that mechanical stimuli can be transmitted directly to the channel via lipid bilayer deformation — in other words, the channel directly responds to changes in membrane tension.
- Golgi tendon organs
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Sensory receptors located at the junction of muscles and tendons that detect muscle tension to generate the sense of proprioception.
- High-speed atomic force microscopy
-
An advanced type of atomic force microscopy that is utilized to probe biological molecules and dynamic processes at high temporal resolution.
- Mechanical allodynia
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A condition where non-painful stimuli, such as light touch or gentle pressure, cause pain.
- Merkel cells
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A specialized type of mechanoreceptor cells in the skin that are involved in touch detection.
- Molecular dynamics simulations
-
Computational techniques that allow the simulation of the interactions of atoms and molecules of a system over a specific period of time through solving classical equations of motion.
- Muscle spindles
-
Sensory receptors within muscles that detect changes in muscle length and the rate of change in length to generate the sense of proprioception.
- Tau value
-
For the inactivating current, the time it takes for the mechanically activated current to decay to about 63.2% of its peak.
- Tenocyte
-
A specialized type of fibroblastic cell found within tendons that has a crucial role in maintaining the extracellular matrix of tendons.
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Xiao, B. Mechanisms of mechanotransduction and physiological roles of PIEZO channels. Nat Rev Mol Cell Biol (2024). https://doi.org/10.1038/s41580-024-00773-5
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DOI: https://doi.org/10.1038/s41580-024-00773-5
