Duret Guillaume, Coffler Samantha, Avant Ben, Kim Wonjune, Peterchev Angel V, Robinson Jacob
bioRxiv. 2025 Feb 8:2025.02.07.636926. doi: 10.1101/2025.02.07.636926.
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.
细胞活动的磁控技术有着广泛的应用，从非侵入性神经刺激到基于细胞的疗法的远程激活。与其他调节细胞活动的方法，如基于已知受体或蛋白质的热和光不同，迄今为止尚未发现磁控通道。因此，细胞活动磁控的有效方法基于能够感应电场的强交变磁场，或基于能将磁能转化为电能、热能或机械能以刺激细胞的材料。在我们对细胞磁响应的研究中，我们发现一种无其他辅助因子的尖峰状人胚肾（HEK）细胞系，使用永磁体时，对在200毫秒内达到最大500毫特斯拉的磁场有反应。这种反应很罕见，大约每50个细胞中有1个，但反应迅速且可重复，在磁场刺激的200毫秒内产生动作电位。磁场刺激比经颅磁刺激（TMS）中使用的磁场慢10000多倍，且感应电场比神经调节所需的电场低一个数量级以上，这表明感应电流不会驱动细胞反应。相反，我们的计算表明，这种反应取决于由TRP相关脂筏的磁转矩激活的机械感受通路。尽管对磁刺激的反应相对罕见，但当细胞形成间隙连接时，磁刺激可以传播到附近细胞，引起组织水平的反应。例如，我们将尖峰状HEK细胞与β胰岛MIN6细胞共培养，发现这种共培养物对磁场的反应是增加胰岛素分泌。总之，这些结果指向一种无需合成纳米颗粒等材料辅助因子即可进行生物活动磁控的方法。通过更好地理解这一机制并增强磁敏感性，有可能使这种方法适用于快速扩展的无线细胞活动调节工具包。
