Parallelized Mechanical Stimulation of Neuronal Calcium Through Cell-Internal Nanomagnetic Forces Provokes Lasting Shifts in the Network Activity State

Neurons differentiate mechanical stimuli force and rate to elicit unique functional responses, driving the need for further tools to generate various mechanical stimuli. Here, cell-internal nanomagnetic forces (iNMF) are introduced by manipulating internalized magnetic nanoparticles with an external magnetic field across cortical neuron networks in vitro. Under iNMF, cortical neurons exhibit calcium (Ca²⁺) influx, leading to modulation of activity observed through Ca²⁺ event rates. Inhibiting particle uptake or altering nanoparticle exposure time reduced the neuronal response to nanomagnetic forces, exposing the requirement of nanoparticle uptake to induce the Ca²⁺ response. In highly active cortical networks, iNMF robustly modulates synchronous network activity, which is lasting and repeatable. Using pharmacological blockers, it is shown that iNMF activates mechanosensitive ion channels to induce the Ca²⁺ influx. Then, in contrast to transient mechanically evoked neuronal activity, iNMF activates Ca²⁺-activated potassium (K_Ca) channels to stabilize the neuronal membrane potential and induce network activity shifts. The findings reveal the potential of magnetic nanoparticle-mediated mechanical stimulation to modulate neuronal circuit dynamics, providing insights into the biophysics of neuronal computation.