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

Lee, Jung Uk; Shin, Wookjin; Lim, Yongjun; Kim, Jungsil; Kim, Woon Ryoung; Kim, Heehun; Lee, Jae Hyun; Cheon, Jinwoo

doi:10.1038/s41563-020-00896-y

Cited by 125 publications

(122 citation statements)

References 48 publications

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“…A similar shape-based approach was described in the work of Lee et al [124]. The authors assembled a complex structure, defined as an m-Torquer, from octahedron magnetite nanoparticles with predefined volume magnetization distributions.…”

Section: Ion Channel Disturbancementioning

confidence: 99%

Nanomaterial Shape Influence on Cell Behavior

Kladko

Falchevskaya

Serov

et al. 2021

IJMS

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Nanomaterials are proven to affect the biological activity of mammalian and microbial cells profoundly. Despite this fact, only surface chemistry, charge, and area are often linked to these phenomena. Moreover, most attention in this field is directed exclusively at nanomaterial cytotoxicity. At the same time, there is a large body of studies showing the influence of nanomaterials on cellular metabolism, proliferation, differentiation, reprogramming, gene transfer, and many other processes. Furthermore, it has been revealed that in all these cases, the shape of the nanomaterial plays a crucial role. In this paper, the mechanisms of nanomaterials shape control, approaches toward its synthesis, and the influence of nanomaterial shape on various biological activities of mammalian and microbial cells, such as proliferation, differentiation, and metabolism, as well as the prospects of this emerging field, are reviewed.

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Section: Ion Channel Disturbancementioning

confidence: 99%

Nanomaterial Shape Influence on Cell Behavior

Kladko

Falchevskaya

Serov

et al. 2021

IJMS

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“…These multi-second latencies prevent precise timing with behavioral or environmental cues that are essential for studying the relationship between neural activity and behavior. Magnetic activation of mechanoreceptors in contact with magnetic particles that move in response to a magnetic field offers a path to faster stimulation 14 , but the in vivo response time remains on the order of several seconds and requires micron-sized particles or aggregates that can be difficult to deliver in vivo 15 .…”

Section: Mainmentioning

confidence: 99%

Sub-second multi-channel magnetic control of select neural circuits in behaving flies

Sebesta

Torres

Wang

et al. 2021

Preprint

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Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or "magnetogenetics" using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.

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“…The strong magnetic fields used by TMS cause undesirable side effects like muscle twitch, facial pain and other discomforts 11 . In the last decade, magnetic approaches with weak magnetic fields by using nanoparticle-based neuronal modulation were developed rapidly 5,[12][13][14][15][16] .…”

Section: Main Textmentioning

confidence: 99%

“…In contrast to PNS, Piezo1/2 expression in CNS neurons is very low. By overexpression Piezo1 in the brain, neurons could be stimulatesd by the torque of 500 nm magnetic nanoparticles with 20 mT magnetic field at 0.5 Hz 16 . However, the potential side effects of overexpression exogeneous gene are still unclear.…”

Section: Main Textmentioning

confidence: 99%

Remote Deep Brain Stimulation by Transgene-free Magnetomechanical Approach

Yen

Cheng

et al. 2021

Preprint

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Various physical stimulation methods are developed to minimize the invasiveness of deep brain stimulation (DBS)1–3. Among them, only magnetic field can penetrate into the biological tissues without scattering or absorption4, which makes it ideal for untethered DBS. Recently developed magnetogenetics have shown the potential of developing treatments for neurological disorders5. However, magnetogenetic approaches have potential side effects from overexpression of exogenous ion channels and gene delivery with viral vectors6,7. Here, we demonstrated that the iron oxide magnetic nanodiscs (~270 nm) can be used as transducers to trigger calcium responses in the wild-type cultured neurons during the application of slow varying weak magnetic fields (50 mT at 10 Hz). Moreover, we identified that the intrinsic mechanosensitive ion channel transient receptor potential canonical (TRPC), which were widely expressed in the brain8, plays the main roles in this magnetomechanical stimulation. Finally, when we applied magnetic fields to the awake mice with magnetic nanodiscs injecting into subthalamic nucleus, the magnetomechanical stimulation triggered neuronal activities in the targeted region and the downstream region. Overall, this research demonstrated a magnetomechanical approach that can be used for wireless neuronal stimulation in vitro and untethered DBS in awake mice in vivo without implants or genetic manipulation.

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

Cited by 125 publications

References 48 publications

Nanomaterial Shape Influence on Cell Behavior

Nanomaterial Shape Influence on Cell Behavior

Sub-second multi-channel magnetic control of select neural circuits in behaving flies

Remote Deep Brain Stimulation by Transgene-free Magnetomechanical Approach

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