Magnetic Vortex Nanodiscs Enable Remote Magnetomechanical Neural Stimulation

Abstract

Magnetic nanomaterials in magnetic fields can serve as versatile transducers for remote interrogation of cell functions. In this study, we leveraged the transition from vortex to in-plane magnetization in iron oxide nanodiscs to modulate the activity of mechanosensory cells. When a vortex configuration of spins is present in magnetic nanomaterials, it enables rapid control over their magnetization direction and magnitude. The vortex configuration manifests in near zero net magnetic moment in the absence of a magnetic field, affording greater colloidal stability of magnetic nanomaterials in suspensions. Together, these properties invite the application of magnetic vortex particles as transducers of externally applied minimally invasive magnetic stimuli in biological systems. Using magnetic modeling and electron holography, we predict and experimentally demonstrate magnetic vortex states in an array of colloidally synthesized magnetite nanodiscs 98–226 nm in diameter. The magnetic nanodiscs applied as transducers of torque for remote control of mechanosensory neurons demonstrated the ability to trigger Ca2+ influx in weak (≤28 mT), slowly varying (≤5 Hz) magnetic fields. The extent of cellular response was determined by the magnetic nanodisc volume and magnetic field conditions. Magnetomechanical activation of a mechanosensitive cation channel TRPV4 (transient receptor potential vanilloid family member 4) exogenously expressed in the nonmechanosensitive HEK293 cells corroborated that the stimulation is mediated by mechanosensitive ion channels. With their large magnetic torques and colloidal stability, magnetic vortex particles may facilitate basic studies of mechanoreception and its applications to control electroactive cells with remote magnetic stimuli.

TRP Channels as Cellular Targets of Particulate Matter

“…The activation of the channels results into a rise in intracellular Ca 2+ concentration, causing depolarization and triggering of specific cellular processes. This method of remotely controlling the cells allows the release of hormones such as corticosterone, epinephrine and norepinephrine has been achieved up to date [36,[75][76][77]. The effect produced depends on the magnetization level (Fe 3 O 4 has higher magnetization than FeO), the strength of the field and the number of NPs [36,77].…”

“…Reaching a high enough concentration of NPs in vivo is a difficult task [76]. Iron oxides can be incorporated with other compounds such as PMAO [36] streptavidin [76], polyethylene [77] and multi-walled carbon nanotubes [75]. It is assumed that the effects of magnetic nanocompounds are rather on the gating of the channel than on the permeability of the lipid bilayer [36].…”

“…The most researched TRP channel in terms of their interaction with PM are TRPV1 and TRPV4. These channels are activated by heating, oxidative stress, osmotic pressure, mechanical perturbations and fatty acid metabolites [32][33][34][35][36][37]. TRPV1 is notably activated by the pungent natural compound capsaicin and by acidosis [38], whereas TRPV4 is best known for being activated by phorbol derivatives (4α-phorbol 12,13-didecanoate, AKA 4αPDD) and the synthetic agonist GSK1016790A [39].…”

Ultrasound neuromodulation through nanobubble-actuated sonogenetics

“…Such companion nanoparticles have been used as mediators to improve the reach, temporal resolution and targeting of various techniques, or to decrease the invasiveness of the treatment's scheme. Noteworthy approaches that have been demonstrated include upconversion nanoparticle-mediated (UCNP) near-infrared optogenetics 1 , gold nanoparticle-assisted photothermal stimulation 2 , and magnetic nanoparticle-based magnetothermal/magnetomechanical stimulation 3,4,5 . Insofar as the goal is to move towards treatments that have high temporal resolution and are as minimally-invasive as achievable, nanoparticle mediators have helped in this regard.…”

Sub-second multi-channel magnetic control of select neural circuits in behaving flies

“…These multi-second latencies prevent precise timing with behavioral or environmental cues that are essential for studying the relationship between neural activity and behavior. Magnetic activation of mechanoreceptors in contact with magnetic particles that move in response to a magnetic field offers a path to faster stimulation 11 , but the in vivo response time remains on the order of several seconds and requires micron-sized particles or aggregates that can be difficult to deliver in vivo 12 .…”