Multimodal Characterization\nof Cortical Neuron Response\nto Permanent Magnetic Field Induced Nanomagnetic Force Maps

Nanomagnetic forces deliver precise mechanical cues to\nbiological\nsystems through the remote pulling of magnetic nanoparticles under\na permanent magnetic field. Cortical neurons respond to nanomagnetic\nforces with cytosolic calcium influx and event rate shifts. However,\nthe underlying consequences of nanomagnetic force modulation on cortical\nneurons remain to be elucidated. Here, we integrate electrophysiological\nand optical recording modalities with nanomagnetic forces to characterize\nthe <i>in vitro</i> functional response to mechanical cues.\nNeurons exposed to chitosan functionalized magnetic nanoparticles\nfor 24 h and then exposed to magnetic fields capable of generating\nforces of 2–160 pN present elevated cytosolic calcium in neurons\nand a time-dynamic electrophysiological spike rate and magnitude response.\nExtracellular recordings with microelectrode arrays revealed a 2–8\npN force-specific increase in electrophysiological spiking with a\ntrend in reduced activity following 2 min of continuous force exposure.\nNanomagnetic forces in the 16–160 pN range produced increased\nelectrophysiological activity and remained excited for up to 4 h under\ncontinuous stimulation before silencing. Furthermore, the neuronal\nresponse to nanomagnetic forces at 16–160 pN can be electrophysiologically\nmediated without calcium influx by altering the magnetic nanoparticle-neuron\ninteractions. These results demonstrate that low pN nanomagnetic forces\nmediate neuronal function and suggest that magnetic nanoparticle interactions\nand force magnitudes can be harnessed to provoke different responses\nin cortical neurons.