Multimodal Characterization of Cortical Neuron Response to Permanent Magnetic Field Induced Nanomagnetic Force Maps

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