GREAT: Wireless magneto-mechanical control of neural activity mediated by magnetic nanodiscs

Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities. Manipulation of brain circuits via direct drug treatment is restricted by the selective permeability of the blood-brain barrier, the rapid clearance of cerebral fluids and the lack of specificity which results in poor response to drugs and undesirable side effects. Electrical stimulation and optogenetics have open the possibility of repairing neural dysfunction through direct control of brain circuit dynamics. However, both technologies require implantable devices that are damaging to biological tissues. Minimally invasive control of cell signaling with magnetic fields is being explored in basic studies of the nervous and immune systems. Wireless schemes based on hysteretic heating of magnetic nanoparticles in high-frequency alternating magnetic fields (AMFs) have already permitted modulation of neural activity and cancer theranostics in vivo. Despite these advances, the potential off-target heating effects and challenges in scaling of high-frequency AMF apparatuses impede universal adoption of magnetic hyperthermia in biomedical research. Here we propose a scalable magneto-mechanical scheme for remote control of neural activity mediated by magnetic nanodisks (MNDs). MNDs will be fabricated by interferance litography and template-assisted physical deposition technique to produce non-toxic MNDs with high colloidal stability. When interfaced with the cell membranes, MNDs will act as transducers of low frequency low amplitude (20-50 mT, 5-10 Hz) magnetic fields into mechanical forces. This technology will be applied to control neural activity in motor neurons isolated from rat spinal cords. In contrast to magneto-thermal approaches, the system proposed here offers straightforward scalability to large volumes, requires significantly lower magnetic energy, and is capable of modulating cell calcium influx without reliance on transgenes.