Elucidating Mechanotransduction Processes During Magnetomechanical Neuromodulation Mediated by Magnetic Nanodiscs.

Purpose: Noninvasive cell-type-specific manipulation of neural signaling is critical in basic neuroscience research and in developing therapies for neurological disorders. Magnetic nanotechnologies have emerged as non-invasive neuromodulation approaches with high spatiotemporal control. We recently developed a wireless force-induced neurostimulation platform utilizing micro-sized magnetic discs (MDs) and low-intensity alternating magnetic fields (AMFs). When targeted to the cell membrane, MDs AMFs-triggered mechanoactuation enhances specific cell membrane receptors resulting in cell depolarization. Although promising, it is critical to understand the role of mechanical forces in magnetomechanical neuromodulation and their transduction to molecular signals for its optimization and future translation. Methods: MDs are fabricated using top-down lithography techniques, functionalized with polymers and antibodies, and characterized for their physical properties. Primary cortical neurons co-cultured with MDs and transmembrane protein chemical inhibitors are subjected to 20 s pulses of weak AMFs (18 mT, 6 Hz). Calcium cell activity is recorded during AMFs stimulation. Results: Neuronal activity in primary rat cortical neurons is evoked by the AMFs-triggered actuation of targeted MDs. Ion channel chemical inhibition suggests that magnetomechanical neuromodulation results from MDs actuation on Piezo1 and TRPC1 mechanosensitive ion channels. The actuation mechanisms depend on MDs size, with cell membrane stretch and stress caused by the MDs torque being the most dominant. Conclusions: Magnetomechanical neuromodulation represents a tremendous potential since it fulfills the requirements of negligible heating (ΔT < 0.1 °C) and weak AMFs (< 100 Hz), which are limiting factors in the development of therapies and the design of clinical equipment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00786-8.