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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 Gd3+. 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.
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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 (KCa) 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.
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- Award ID(s):
- 1846271
- PAR ID:
- 10636583
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Small
- Volume:
- 21
- Issue:
- 1
- ISSN:
- 1613-6810
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/smll.202406678
