Magnetic activation of electrically active cells

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Abstract
Magnetic control of cell activity has applications ranging from non-invasive neurostimulation to remote activation of cell-based therapies. Unlike other methods of regulating cell activity like heat and light, which are based on known receptors or proteins, no magnetically gated channel has been identified to date. As a result, effective approaches for magnetic control of cell activity are based on strong alternating magnetic fields able to induce electric fields or materials that convert magnetic energy into electrical, thermal, or mechanical energy to stimulate cells. In our investigations of magnetic cell responses, we found that a spiking HEK cell line with no other co-factors responds to a magnetic field that reaches a maximum of 500 mT within 200 ms using a permanent magnet. The response is rare, approximately 1 in 50 cells, but is fast and reproducible, generating an action potential within 200 ms of magnetic field stimulation. The magnetic field stimulation is over 10,000 times slower than the magnetic fields used in transcranial magnetic stimulation (TMS) and the induced electric field is more than an order of magnitude lower than necessary for neuromodulation, suggesting that induced electric currents do not drive the cell response. Instead, our calculation suggests that this response depends on mechanoreception pathways activated by the magnetic torque of TRP-associated lipid rafts. Despite the relatively rare response to magnetic stimulation, when cells form gap junctions, the magnetic stimulation can propagate to nearby cells, causing tissue-level responses. As an example, we co-cultured spiking HEK cells with beta-pancreatic MIN6 cells and found that this co-culture responds to magnetic fields by increasing insulin production. Together, these results point toward a method for the magnetic control of biological activity without the need for a material co-factor such as synthetic nanoparticles. By better understanding this mechanism and enriching for magneto-sensitivity it may be possible to adapt this approach to the rapidly expanding tool kit for wireless cell activity regulation.

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