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Biology subjects

Signorelli, L.

Publications and source records attributed to Signorelli, L..

3 recordsLinked to original sources

Remote magnetomechanical neuromodulation uncovers a novel therapeutic mechanism for alleviating Parkinsonian symptoms in freely moving mice

To overcome the limitations of invasive neuromodulation systems, we introduce a wireless magnetomechanical approach for remote, minimally invasive deep brain stimulation (DBS) without chronically implanted electrodes. This method leverages biocompatible nanoscale magnetite nanodiscs (MNDs) with ground vortex magnetisation, which undergo in-plane transitions under low-frequency alternating magnetic fields, thereby generating localised piconewton-scale torques. These torques engage endogenous mechanosensory pathways to modulate neural activity, enabling reversible stimulation without the need for genetic modifications. Calcium imaging validated the rapid neuromodulatory effects of MNDs in vitro and ex vivo, which motivated the subsequent application of magnetomechanical DBS to the subthalamic nucleus in mice. We demonstrated the remote control of motor behaviour in wild-type mice and significant restoration of motor function in a severe hemiparkinsonian model. This study established the first wireless therapeutic magnetomechanical neuromodulation platform that leverages biocompatible nanomaterials and endogenous mechanosensory ion channels, representing a promising step toward untethered, clinically translatable neurotechnology.

neuroscience↗

Biocompatible PVDF Nanofibers with Embedded Magnetite Nanodiscs Enable Wireless Magnetoelectric Neuromodulation

Wireless neuromodulation technologies aim to eliminate the need for invasive hardware and enhance tissue compatibility. Magnetoelectric (ME) materials enable magnetic field-induced electrical stimulation, offering a minimally invasive neural activation. However, conventional ME systems use rigid ceramic components with limited biocompatibility. Here, we report a flexible, predominantly organic ME platform composed of polyvinylidene fluoride (PVDF) nanofibers embedded with anisotropic magnetite nanodiscs (MNDs). These MNDs were selected for their unique ability to exert magnetic torque due to vortex magnetization, and their intrinsic magnetostrictive behaviour. The resulting ME fibers preserve the piezoelectric {beta}-phase of PVDF and exhibit magnetoelectric voltage coefficient of 1.26 Vcm-{superscript 1}Oe-{superscript 1}. We compare two magnetic activation strategies; torque-based and high-frequency magnetostriction, finding that magnetostriction more effectively triggers neuronal responses. In vitro calcium imaging reveals robust activation in primary cortical neurons cultured on ME fibers. Biocompatibility post-stimulation was confirmed on ex vivo human brain tissue, with no increased cell death. Implanted into the premotor cortex of freely moving mice, the fibers enabled wireless modulation of motor behaviour under an alternating magnetic field. This work presents the first demonstration of wireless magnetoelectric neuromodulation using soft, biocompatible fiber composites, paving the way for future bioelectronic interfaces free from rigid components and tethered systems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/660052v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@7868e7org.highwire.dtl.DTLVardef@12f32a7org.highwire.dtl.DTLVardef@1a6a7e4org.highwire.dtl.DTLVardef@5876e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Magnetoelectric Nanodiscs Enable Wireless Transgene-Free Neuromodulation

Deep-brain stimulation (DBS) with implanted electrodes revolutionized treatment of movement disorders and empowered neuroscience studies. Identifying less invasive alternatives to DBS may further extend its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials offers an alternative to invasive DBS. Here, we synthesize magnetoelectric nanodiscs (MENDs) with a core-double shell Fe3O4-CoFe2O4-BaTiO3 architecture with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 {micro}g/mm2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization, which combined with cable theory, corroborates our findings in vitro and informs magnetoelectric stimulation in vivo. MENDs injected into the ventral tegmental area of genetically intact mice at concentrations of 1 mg/mL enable remote control of reward behavior, setting the stage for mechanistic optimization of magnetoelectric neuromodulation and inspiring its future applications in fundamental and translational neuroscience.

bioengineering↗