Abstract
Among physical stimulation modalities, magnetism has clear advantages, such as deep penetration and untethered interventions in biological subjects. However, some of the working principles and effectiveness of existing magnetic neurostimulation approaches have been challenged, leaving questions to be answered. Here we introduce m-Torquer, a magnetic toolkit that mimics magnetoreception in nature. It comprises a nanoscale magnetic torque actuator and a circular magnet array, which deliver piconewton-scale forces to cells over a working range of ~70 cm. With m-Torquer, stimulation of neurons expressing bona fide mechanosensitive ion channel Piezo1 enables consistent and reproducible neuromodulation in freely moving mice. With its long working distance and cellular targeting capability, m-Torquer provides versatility in its use, which can range from single cells to in vivo systems, with the potential application in large animals such as primates.
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Data availability
The statistical data are provided with the paper as source data. Additional data that support the findings of this study are available from the corresponding authors on reasonable request.
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Acknowledgements
Myc897–Piezo1 (Myc tag at the 897 N-terminal residue of Piezo1) in pcDNA3.1 was kindly provided by A. Patapoutian (The Scripps Research Institute, La Jolla, CA, USA). We thank E. Chung, J. Kim, J.-w. Kim, and C. Mikuni for initial help and discussions on this research. This work was supported by the Institute for Basic Science (IBS-R026-D1).
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J.-u.L. performed the overall experiments. Y.L. provided magnetic nanoparticles. J.K. and H.K. performed magnetic field simulation. W.S. and W.R.K. performed in vitro and in vivo experiments. J.-H.L. and J.C. wrote the manuscript. J.C. conceived and supervised the project.
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Supplementary Information
Descriptions of Supplementary Videos 1–4, Supplementary Figs. 1–22, Table 1, and Notes 1 and 2.
Supplementary Video 1
Representative fluorescence video of suspended m-Torquer (in 98% glycerol) and bound m-Torquer on cell membrane in rotating magnetic field.
Supplementary Video 2
In situ calcium influx induced by m-Torquer in Piezo1-expressing neuron.
Supplementary Video 3
In situ calcium influx of repetitive stimulation of Piezo1.
Supplementary Video 4
Mouse behaviour control experiment with freely moving mouse.
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Source Data Fig. 4
Statistical source data.
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Statistical source data.
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Lee, Ju., Shin, W., Lim, Y. et al. Non-contact long-range magnetic stimulation of mechanosensitive ion channels in freely moving animals. Nat. Mater. 20, 1029–1036 (2021). https://doi.org/10.1038/s41563-020-00896-y
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DOI: https://doi.org/10.1038/s41563-020-00896-y
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