Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields

Krishnan, Vijai; Park, Sarah A.; Shin, Samuel S.; Alon, Lina; Tressler, Caitlin M.; Stokes, William S.; Banerjee, Jineta; Sorrell, Mary E.; Tian, Yuemin; Fridman, Gene Y.; Celnik, Pablo; Pevsner, Jonathan; Guggino, William B.; Gilad, Assaf A.; Pelled, Galit

doi:10.1038/s41598-018-27087-9

Cited by 44 publications

(78 citation statements)

References 59 publications

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“…The HEK293T cells were transfected with a pcDNA3.1 vector construct containing the EPG gene under the CMV promoter pcDNA3.1-EPG+GFP [32] ( Figure 1A). Figure 1B shows the schematic drawing of the biological circuit.…”

Section: Resultsmentioning

confidence: 99%

“…The measured responded cells were described as a numeric value at a given time point. Responding cells were determined using the following equation (Equation 1) [32]:…”

Section: Cell Identificationmentioning

confidence: 99%

“…This study utilizes the electromagnetic perceptive gene (EPG) that was isolated from Kryptopterus bicirrhis (glass catfish) and was demonstrated to respond to electromagnetic fields (EMF) [32]. Previous results have shown that EPG gene activation by an electromagnetic stimulus is primarily associated with an increase in intracellular calcium, [Ca 2+ ] i Activation of EPG by electromagnetic stimulus has been successfully reported in in-vivo (rodent) and in-vitro models (HEK cells, primary cortical neurons).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Electromagnetic Perceptive Gene Using Ferromagnetic Particles for the External Control of Calcium Ion Transport

et al. 2020

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Developing synthetic biological devices to allow the noninvasive control of cell fate and function, in vivo can potentially revolutionize the field of regenerative medicine. To address this unmet need, we designed an artificial biological “switch” that consists of two parts: (1) the electromagnetic perceptive gene (EPG) and (2) magnetic particles. Our group has recently cloned the EPG from the Kryptopterus bicirrhis (glass catfish). The EPG gene encodes a putative membrane-associated protein that responds to electromagnetic fields (EMFs). This gene’s primary mechanism of action is to raise the intracellular calcium levels or change in flux through EMF stimulation. Here, we developed a system for the remote regulation of [Ca2+]i (i.e., intracellular calcium ion concentration) using streptavidin-coated ferromagnetic particles (FMPs) under a magnetic field. The results demonstrated that the EPG-FMPs can be used as a molecular calcium switch to express target proteins. This technology has the potential for controlled gene expression, drug delivery, and drug developments.

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Section: Resultsmentioning

confidence: 99%

“…The measured responded cells were described as a numeric value at a given time point. Responding cells were determined using the following equation (Equation 1) [32]:…”

Section: Cell Identificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of Electromagnetic Perceptive Gene Using Ferromagnetic Particles for the External Control of Calcium Ion Transport

et al. 2020

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“…However, one of the drawbacks of this technology is the requirement to deliver the light directly into the target neural population. Here we tested if neuromodulation via the magnetic sensitive protein EPG, which provides cell and temporal specificity while being activated remotely via non-invasive electromagnetic fields 53 , can be utilized to restore cortical excitability and achieve similar sensorimotor outcomes compared to rTMS. The results demonstrate that daily magnetic activation of EPG improved sensory, motor, and an overall well-being of the injured rats in a battery of behavioral tests that were performed up to 4 weeks after the EPG treatment ended.…”

Section: Discussionmentioning

confidence: 99%

“…One of these technologies, magnetic manipulation by the electromagnetic preceptive gene (EPG), allows non-invasive and cell-specific neuromodulation using external magnetic fields. EPG is a protein that is sensitive to electromagnetic fields which was recently identified in the fish Kryptopterus bicirrhis 43 . Recent work had demonstrated that calcium imaging in mammalian cells and cultured neurons expressing EPG activated remotely by magnetic fields led to increases in intracellular calcium concentrations, indicative of cellular excitability.…”

Section: Introductionmentioning

confidence: 99%

Non-invasive neuromodulation using rTMS and the Electromagnetic-Perceptive Gene (EPG) facilitates plasticity after nerve injury

Cywiak

Ashbaugh

Metto

et al. 2019

Preprint

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Peripheral nerve injury leads to altered cortical excitation-inhibition balance which is associated with sensory dysfunctions. We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which has shown to induce neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from Kryptopterrus bicirrhis and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. A battery of behavioral tests, fMRI and immunochemistry were performed in the weeks following limb denervation in rats. The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The study also identifies the acute post-injury phase as a critical time for intervention. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.

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Enhancing c‐fosmRNA Expression in Primary Cortical Cell Cultures with a Dynamic Magnetic Fields Device

Shibata,

Ihara,

Kirihara

et al. 2023

IEEJ Transactions Elec Engng

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Magnetic fields have the potential to impact biological systems and trigger various biological responses. However, the mechanisms underlying dynamic magnetic fields (DMFs), which are created by rotating magnets based on Arago's disk principle and include eddy currents, Lorentz forces, and magnetic fields, are not well understood. This study aims to investigate the effects of DMFs on gene expression in primary cultured cortical cells. To simulate DMFs, rotating magnets were used to confirm magnetic flux density, current density, and Lorentz force. Primary cortical cell cultures were then exposed to moderate‐intensity DMFs with a frequency of 40 Hz for 1 h per day over 3 days. The expression of neuroplasticity‐related immediate early genes, including proto‐oncogene c‐fos, activity‐regulated cytoskeleton‐associated protein (Arc) and brain‐derived neurotrophic factor (BDNF) were quantified. The simulation of DMFs generated a periodic magnetic flux density of up to 131 mT, a periodic current density of up to 1.69 A/m2, and a periodic Lorentz force of up to 0.88 nN in the dish. Exposure to DMFs increased c‐fos mRNA expression in primary cortical cell cultures, but did not affect Arc and BDNF expression. The findings suggest that exposure of DMFs in the gamma frequency range, which may be regulated by voltage‐, mechanical‐, and magnetic flux‐sensitive ion channels, could enhance c‐fos expression in primary cortical cell cultures. The device using rotating magnets has the potential to facilitate the development of a cost‐effective and user‐friendly cell culture system based on the principle of Arago's disk. © 2023 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.

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Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields

Cited by 44 publications

References 59 publications

Regulation of Electromagnetic Perceptive Gene Using Ferromagnetic Particles for the External Control of Calcium Ion Transport

Regulation of Electromagnetic Perceptive Gene Using Ferromagnetic Particles for the External Control of Calcium Ion Transport

Non-invasive neuromodulation using rTMS and the Electromagnetic-Perceptive Gene (EPG) facilitates plasticity after nerve injury

Enhancing c‐fosmRNA Expression in Primary Cortical Cell Cultures with a Dynamic Magnetic Fields Device

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