Targeted Magnetic Vortex Disc Delivery Enables Magneto-Mechanical Control of Mouse Behavior

Low frequency magnetic fields pass through the body without attenuation, enabling the delivery of magnetic stimuli to deep tissue structures. We and others have previously demonstrated that magnetic nanodiscs (MNDs) composed of iron oxide can exert force on mechanoreceptors and control Ca²⁺ influx into sensory neurons in dorsal root ganglia and human embryonic kidney cells (HEK293) engineered to express the putative mechanoreceptor TRPV4¹. These prior studies have, however, relied on electrostatic targeting of the MNDs to cell membranes, and consequently magnetomechanical modulation lacked specificity to a particular cell type.<br/><br/>Here, we demonstrate the functionalization of MNDs with Benzylguanine (BG), a moiety that specifically binds to the genetically expressed SNAP tag to enable targeted delivery of MNDs to mechanosensitized cells. We employ a slowly varying alternating magnetic field to deliver the stimuli to the MNDs. Using Ca²⁺-imaging, we confirm the targeted stimulation of HEK293 cells and primary hippocampal neurons engineered to express mechanoreceptors. We further investigate the effects of the magnetomechanical stimulation on the cell membrane potential using the patch clamp electrophysiology.<br/><br/>Finally, we explore the possibility of magnetomechanical stimulation as a means to control neuronal activity and behavior in untethered freely-moving rodents. We anticipate that magnetomechanical stimulation will complement an existing array of tools aimed at connecting molecular and circuit function in the context of behavior.<br/><br/>1. Gregurec et al, ACS Nano 2020.