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Non-contact long-range magnetic stimulation of mechanosensitive ion channels in freely moving animals


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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Fig. 1: Schematic of the nanoscale magnetic torquer (m-Torquer) system.
Fig. 2: Magnetically anisotropic octahedral nanoparticles and their assembly into m-Torquer.
Fig. 3: Configurations of the CMA to generate uniform magnetic fields and obtain biologically important forces with an effective distance.
Fig. 4: Magnetomechanical gating of Piezo1 ion channel in cultured neurons with m-Torquer system.
Fig. 5: Long-distance in vivo neuromodulation with m-Torquer in freely moving mice.

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.


  1. 1.

    Fenno, L., Yizhar, O. & Deisseroth, K. The development and application of optogenetics. Annu. Rev. Neurosci. 34, 389–412 (2011).

    CAS  Article  Google Scholar 

  2. 2.

    Hong, G. et al. A method for single-neuron chronic recording from the retina in awake mice. Science 360, 1447–1451 (2018).

    CAS  Article  Google Scholar 

  3. 3.

    Munshi, R. et al. Magnetothermal genetic deep brain stimulation of motor behaviors in awake, freely moving mice. eLife 6, e27069 (2017).

    Article  Google Scholar 

  4. 4.

    Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).

    CAS  Article  Google Scholar 

  5. 5.

    Beurrier, C., Bioulac, B., Audin, J. & Hammond, C. High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J. Neurophysiol. 85, 1351–1356 (2001).

    CAS  Article  Google Scholar 

  6. 6.

    Huang, H., Delikanli, S., Zeng, H., Ferkey, D. M. & Pralle, A. Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nat. Nanotechnol. 5, 602–606 (2010).

    CAS  Article  Google Scholar 

  7. 7.

    Chen, R., Romero, G., Christiansen, M. G., Mohr, A. & Anikeeva, P. Wireless magnetothermal deep brain stimulation. Science 347, 1477–1480 (2015).

    CAS  Article  Google Scholar 

  8. 8.

    Delmas, P., Hao, J. & Rodat-Despoix, L. Molecular mechanisms of mechanotransduction in mammalian sensory neurons. Nat. Rev. Neurosci. 12, 139–153 (2011).

    CAS  Article  Google Scholar 

  9. 9.

    Huse, M. Mechanical forces in the immune system. Nat. Rev. Immunol. 17, 679–690 (2017).

    CAS  Article  Google Scholar 

  10. 10.

    Li, T. L. et al. Engineering a genetically encoded magnetic protein crystal. Nano Lett. 19, 6955–6963 (2019).

    CAS  Article  Google Scholar 

  11. 11.

    Gregurec, D. et al. Magnetic vortex nanodiscs enable remote magnetomechanical neural stimulation. ACS Nano 14, 8036–8045 (2020).

    CAS  Article  Google Scholar 

  12. 12.

    Christiansen, M. G., Senko, A. W. & Anikeeva, P. Magnetic strategies for nervous system control. Annu. Rev. Neurosci. 42, 271–293 (2019).

    CAS  Article  Google Scholar 

  13. 13.

    Wheeler, M. A. et al. Genetically targeted magnetic control of the nervous system. Nat. Neurosci. 19, 756–761 (2016).

    CAS  Article  Google Scholar 

  14. 14.

    Meister, M. Physical limits to magnetogenetics. eLife 5, e17210 (2016).

    Article  CAS  Google Scholar 

  15. 15.

    Xu, F. X. et al. Magneto is ineffective in controlling electrical properties of cerebellar Purkinje cells. Nat. Neurosci. (2019).

  16. 16.

    Cullity, B. D. & Graham, C. D. Introduction to Magnetic Materials 2nd edn (IEEE/Wiley, 2009).

  17. 17.

    Strick, T. R., Allemand, J. F., Bensimon, D., Bensimon, A. & Croquette, V. The elasticity of a single supercoiled DNA molecule. Science 271, 1835–1837 (1996).

    CAS  Article  Google Scholar 

  18. 18.

    Lipfert, J., Kerssemakers, J. W., Jager, T. & Dekker, N. H. Magnetic torque tweezers: measuring torsional stiffness in DNA and RecA-DNA filaments. Nat. Methods 7, 977–980 (2010).

    CAS  Article  Google Scholar 

  19. 19.

    Wang, N., Butler, J. P. & Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127 (1993).

    CAS  Article  Google Scholar 

  20. 20.

    Lipfert, J., van Oene, M. M., Lee, M., Pedaci, F. & Dekker, N. H. Torque spectroscopy for the study of rotary motion in biological systems. Chem. Rev. 115, 1449–1474 (2015).

    CAS  Article  Google Scholar 

  21. 21.

    Lamb, H. Hydrodynamics 6th edn (Dover Publications, 1945).

  22. 22.

    Romano, G., Sacconi, L., Capitanio, M. & Pavone, F. S. Force and torque measurements using magnetic micro beads for single molecule biophysics. Opt. Commun. 215, 323–331 (2003).

    CAS  Article  Google Scholar 

  23. 23.

    Morimatsu, M., Mekhdjian, A. H., Adhikari, A. S. & Dunn, A. R. Molecular tension sensors report forces generated by single integrin molecules in living cells. Nano Lett. 13, 3985–3989 (2013).

    CAS  Article  Google Scholar 

  24. 24.

    Seo, D. et al. A mechanogenetic toolkit for interrogating cell signaling in space and time. Cell 165, 1507–1518 (2016).

    CAS  Article  Google Scholar 

  25. 25.

    Yao, M. et al. Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. Sci. Rep. 4, 4610 (2014).

    Article  CAS  Google Scholar 

  26. 26.

    Svoboda, K. & Block, S. M. Force and velocity measured for single kinesin molecules. Cell 77, 773–784 (1994).

    CAS  Article  Google Scholar 

  27. 27.

    Corey, D. P. & Howard, J. Models for ion channel gating with compliant states. Biophys. J. 66, 1254–1257 (1994).

    CAS  Article  Google Scholar 

  28. 28.

    Kim, D. H. et al. Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction. Nat. Mater. 9, 165–171 (2010).

    CAS  Article  Google Scholar 

  29. 29.

    Shen, Y. et al. Elongated nanoparticle aggregates in cancer cells for mechanical destruction with low frequency rotating magnetic field. Theranostics 7, 1735–1748 (2017).

    CAS  Article  Google Scholar 

  30. 30.

    Kole, K. et al. Assessing the utility of Magneto to control neuronal excitability in the somatosensory cortex. Nat. Neurosci. (2019).

  31. 31.

    Wang, G. et al. Revaluation of magnetic properties of Magneto. Nat. Neurosci. (2019).

  32. 32.

    Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010).

    CAS  Article  Google Scholar 

  33. 33.

    Ranade, S. S., Syeda, R. & Patapoutian, A. Mechanically activated ion channels. Neuron 87, 1162–1179 (2015).

    CAS  Article  Google Scholar 

  34. 34.

    Coste, B. et al. Piezo1 ion channel pore properties are dictated by C-terminal region. Nat. Commun. 6, 7223 (2015).

    Article  Google Scholar 

  35. 35.

    Adamantidis, A. R., Zhang, F., Aravanis, A. M., Deisseroth, K. & de Lecea, L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450, 420–424 (2007).

    CAS  Article  Google Scholar 

  36. 36.

    Sheng, M. & Greenberg, M. E. The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 4, 477–485 (1990).

    CAS  Article  Google Scholar 

  37. 37.

    Covington, H. E. R. et al. Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J. Neurosci. 30, 16082–16090 (2010).

    CAS  Article  Google Scholar 

  38. 38.

    Howard, J. & Hudspeth, A. J. Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the bullfrog’s saccular hair cell. Neuron 1, 189–199 (1988).

    CAS  Article  Google Scholar 

  39. 39.

    Sen, S., Subramanian, S. & Discher, D. E. Indentation and adhesive probing of a cell membrane with AFM: theoretical model and experiments. Biophys. J. 89, 3203–3213 (2005).

    CAS  Article  Google Scholar 

  40. 40.

    Airan, R. D., Thompson, K. R., Fenno, L. E., Bernstein, H. & Deisseroth, K. Temporally precise in vivo control of intracellular signalling. Nature 458, 1025–1029 (2009).

    CAS  Article  Google Scholar 

  41. 41.

    Gradinaru, V. et al. Targeting and readout strategies for fast optical neural control in vitro and in vivo. J. Neurosci. 27, 14231–14238 (2007).

    CAS  Article  Google Scholar 

  42. 42.

    Ranade, S. S. et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516, 121–125 (2014).

    CAS  Article  Google Scholar 

  43. 43.

    Mammoto, T. & Ingber, D. E. Mechanical control of tissue and organ development. Development 137, 1407–1420 (2010).

    CAS  Article  Google Scholar 

  44. 44.

    Jeanes, A., Gottardi, C. J. & Yap, A. S. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27, 6920–6929 (2008).

    CAS  Article  Google Scholar 

  45. 45.

    Jang, J. T. et al. Critical enhancements of MRI contrast and hyperthermic effects by dopant-controlled magnetic nanoparticles. Angew. Chem. Int. Ed. 48, 1234–1238 (2009).

    CAS  Article  Google Scholar 

  46. 46.

    Jewett, J. C. & Bertozzi, C. R. Cu-free click cycloaddition reactions in chemical biology. Chem. Soc. Rev. 39, 1272–1279 (2010).

    CAS  Article  Google Scholar 

  47. 47.

    Kim, J. W. et al. Single-cell mechanogenetics using monovalent magnetoplasmonic nanoparticles. Nat. Protoc. 12, 1871–1889 (2017).

    CAS  Article  Google Scholar 

  48. 48.

    Mittereder, N., March, K. L. & Trapnell, B. C. Evaluation of the concentration and bioactivity of adenovirus vectors for gene therapy. J. Virol. 70, 7498–7509 (1996).

    CAS  Article  Google Scholar 

  49. 49.

    Shin, W. et al. Identification of Ras-degrading small molecules that inhibit the transformation of colorectal cancer cells independent of beta-catenin signaling. Exp. Mol. Med. 50, 71 (2018).

    Google Scholar 

  50. 50.

    Dong, H. W. Allen Reference Atlas: A Digital Color Brain Atlas of the C57Black/6J Male Mouse (Wiley, 2008).

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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).

Author information




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.

Corresponding author

Correspondence to Jinwoo Cheon.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Descriptions of Supplementary Videos 1–4, Supplementary Figs. 1–22, Table 1, and Notes 1 and 2.

Reporting Summary

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.

Source data

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Fig. 5

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. (2021).

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