| Autor: |
Young MN; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710., Sindoni MJ; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710., Lewis AH; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710., Zauscher S; Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27710., Grandl J; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710. |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Feb 21; Vol. 120 (8), pp. e2215747120. Date of Electronic Publication: 2023 Feb 16. |
| DOI: |
10.1073/pnas.2215747120 |
| Abstrakt: |
Cells throughout the human body detect mechanical forces. While it is known that the rapid (millisecond) detection of mechanical forces is mediated by force-gated ion channels, a detailed quantitative understanding of cells as sensors of mechanical energy is still lacking. Here, we combine atomic force microscopy with patch-clamp electrophysiology to determine the physical limits of cells expressing the force-gated ion channels (FGICs) Piezo1, Piezo2, TREK1, and TRAAK. We find that, depending on the ion channel expressed, cells can function either as proportional or nonlinear transducers of mechanical energy and detect mechanical energies as little as ~100 fJ, with a resolution of up to ~1 fJ. These specific energetic values depend on cell size, channel density, and cytoskeletal architecture. We also make the surprising discovery that cells can transduce forces either nearly instantaneously (<1 ms) or with a substantial time delay (~10 ms). Using a chimeric experimental approach and simulations, we show how such delays can emerge from channel-intrinsic properties and the slow diffusion of tension in the membrane. Overall, our experiments reveal the capabilities and limits of cellular mechanosensing and provide insights into molecular mechanisms that different cell types may employ to specialize for their distinct physiological roles. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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