Wireless Force‐Inducing Neuronal Stimulation Mediated by High Magnetic Moment Microdiscs

Abstract

Noninvasive manipulation of cell signaling is critical in basic neuroscience research and in developing therapies for neurological disorders and psychiatric conditions. Here, the wireless force-induced stimulation of primary neuronal circuits through mechanotransduction mediated by magnetic microdiscs (MMDs) under applied low-intensity and low-frequency alternating magnetic fields (AMFs), is described. MMDs are fabricated by top-down lithography techniques that allow for cost-effective mass production of biocompatible MMDs with high saturation and zero magnetic magnetic moment at remanence. MMDs are utilized as transducers of AMFs into mechanical forces. When MMDs are exposed to primary rat neuronal circuits, their magneto-mechanical actuation triggers the response of specific mechanosensitive ion channels expressed on the cell membranes activating ≈50% of hippocampal and ≈90% of cortical neurons subjected to the treatment. Mechanotransduction is confirmed by the inhibition of mechanosensitive transmembrane channels with Gd 3+ . Mechanotransduction mediated by MMDs cause no cytotoxic effect to neuronal cultures. This technology fulfills the requirements of cell-type specificity and weak magnetic fields, two limiting factors in the development of noninvasive neuromodulation therapies and clinical equipment design. Moreover, high efficiency and long-lasting stimulations are successfully achieved. This research represents a fundamental step forward for magneto-mechanical control of neural activity using disc-shaped micromaterials with tailored magnetic properties.

On‐Demand Chemomagnetic Modulation of Striatal Neurons Facilitated by Hybrid Magnetic Nanoparticles

“…Fluorescence Calcium Imaging Video Analysis: Videos were analyzed by adapting previously reported protocol for data analysis on calcium fluorescent image series. [23,47] Briefly, the fluorescence videos recorded were extracted as mp4 files for analysis. Photoshop was used to calibrate for brightness and contrast and export to image sequence files.…”

Conductive Conjugated Polymer Nanocapacitors for Localized Electrical Neurostimulation

“…Instead, it might be taken to show time-integrated levels of neuronal activity. An automated code was generated in MATLAB to analyze the fluorescence intensity traces of neurons in each video . Three different videos containing 300–500 neurons were analyzed for each condition.…”

“…The analysis was performed using ImageJ functions to subtract the background and measure the fluorescence intensity. 10 Time resolution of fluorescence microscopy was insufficient to be interpreted as resolving individual spikes. Instead, it might be taken to show time-integrated levels of neuronal activity.…”

“…8 Nanotechnology advances are enabling new neuromodulation modalities with deeper penetration, less invasiveness, improved biointerfaces, and higher spatiotemporal precision. 9 Wireless neuronal stimulation has recently been achieved using nanotechnology approaches like magnetomechanical actuation by magnetic discs, 10,11 magnetothermal transduction by magnetic nanoparticles, 12,13 chemomagnetic approaches, 14,15 photother-mal polymeric nanotransducers, 16 electric field generation using piezoelectric nanomaterials, 17 and photovoltaic effects from conjugated conductive polymers 18 or magnetoelectric materials. 19,20 In this vein, conjugated conductive polymers are receiving increasing attention due to their electrical and ionic conductivity, which make them ideal for neuronal stimulation.…”

Magnetic nanomaterials for wireless thermal and mechanical neuromodulation

“…The group applied this approach in the motor cortex of mice and demonstrated activation at distances of up to 70 cm ( Lee et al., 2021 ). The demonstration of long-range and precisely tuned mechanical stimulus on mechanosensitive ion channels by these groups, started new studies to explore macroscale anisotropic materials for non-invasive mechanotransduction ( Collier et al., 2022 ), and are used as robust tools to explore endogenous mechanosensitivity in the brain ( Su et al., 2021 ).…”