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Modulating cell signalling in vivo with magnetic nanotransducers

Abstract

Weak magnetic fields offer nearly lossless transmission of signals within biological tissue. Magnetic nanomaterials are capable of transducing magnetic fields into a range of biologically relevant signals in vitro and in vivo. These nanotransducers have recently enabled magnetic control of cellular processes, from neuronal firing and gene expression to programmed apoptosis. Effective implementation of magnetically controlled cellular signalling relies on careful tailoring of magnetic nanotransducers and magnetic fields to the responses of the intended molecular targets. This Primer discusses the versatility of magnetic modulation modalities and offers practical guidelines for selection of appropriate materials and field parameters, with a particular focus on applications in neuroscience. With recent developments in magnetic instrumentation and nanoparticle chemistries, including those that are commercially available, magnetic approaches promise to empower research aimed at connecting molecular and cellular signalling to physiology and behaviour in untethered moving subjects.

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Fig. 1: Magnetic transduction mechanisms.
Fig. 2: Magnetic neuromodulation workflow.
Fig. 3: Chemical and physical analysis of MNPs used for magneto-thermal modulation.
Fig. 4: Chemical, physical and targeting properties of magneto-mechanical nanotransducers.
Fig. 5: An in vitro panel for magneto-thermal activation and silencing of neurons.
Fig. 6: Magneto-thermal and chemomagnetic control of behaviour and physiology: examples of data sets.
Fig. 7: Applications of magneto-mechanical stimulation to trigger neuronal firing in vitro and in vivo.

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Acknowledgements

The authors thank D. Bono, Y. J. Kim, K. Nagao and D. Rosenfeld for the fruitful discussions of magnetic instrumentation, magnetic nanomaterials chemistry and biological applications of magnetic modulation. P.A. and A.P. thank M. Shapiro, J. Cheon, J. Robinson, M. Christiansen and G. Varnavides for their insights into magneto-thermal modulation at the nanoscale.

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Authors and Affiliations

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Contributions

Introduction (G.R.,J.P., F.K., A.P. and P.A.); Experimentation (G.R., J.P., F.K., A.P. and P.A.); Results (G.R., J.P., F.K., A.P. and P.A.); Applications (G.R., J.P., F.K., A.P. and P.A.); Reproducibility and data deposition (G.R., J.P., F.K., A.P. and P.A.); Limitations and optimizations (G.R., J.P., F.K., A.P. and P.A.); Outlook (G.R., A.P. and P.A.); Overview of the Primer (G.R., J.P., F.K., A.P. and P.A.).

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Correspondence to Gabriela Romero, Arnd Pralle or Polina Anikeeva.

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Nature Reviews Methods Primers thanks Gianni Ciofani and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Magnetic modulation

Control of cellular processes or animal behaviour by methods based on the application of magnetic fields.

Transcranial magnetic stimulation

A non-invasive therapeutic and diagnostic method explored as a treatment for neurological and psychiatric conditions based on the electromagnetic induction of local currents in targeted brain regions by externally applied pulsed magnetic fields.

Transducers

Devices to convert one type of signal into another. In this Primer, used to define nanoparticles converting magnetic field energy into other physical stimuli such as heat, force or electric fields.

Magnetosomes

Magnetic iron oxide or iron sulfide nanoparticles enclosed in a biomolecular membrane enabling magnetotactic bacteria to orient along the Earth’s magnetic field lines.

Superparamagnetic nanoparticles

Magnetic nanoparticles (MNPs) whose magnetization in the absence of a magnetic field rotates freely resulting in net-zero magnetization of particle ensembles. Application of a weak magnetic field, however, endows these particles with magnetization response commensurate with magnetic properties of the material that the particles are composed of.

Eddy currents

Electric current loops induced in a conductor surface by a changing magnetic field.

Magneto-mechanical torque

A torque exerted when a magnetic object rotates around an axis to align its magnetic moment with the applied magnetic field direction.

Ferromagnetic

Magnetic materials with high susceptibility to magnetization and the strength of the magnetizing applied field, in which magnetization persists after removal of the magnetic field.

Ferrimagnetic

Magnetic materials comprising two crystalline sublattices with opposing but not equal magnetic moments. In these materials, magnetization persists after the removal of the applied magnetic field, although its values are typically lower than that for ferromagnetic materials.

Brownian relaxation

Magnetic relaxation due to rotational diffusion of magnetic nanoparticles (MNPs) in a liquid.

Neél magnetization relaxation

Magnetic relaxation caused by the reorientation of the magnetization vector inside magnetic nanoparticles (MNPs) without their physical rotation.

Optogenetics

A technique that employs light as an external stimulus to control biological activity in cells genetically modified to express light-sensitive ion channels.

Fibre photometry

A technique using an optical fibre to collect fluorescence from tissues in vivo frequently used in neuroscience to record fluorescence changes of activity indicators.

Subthalamic nucleus

A brain region that is part of the basal ganglia in the subthalamus that is targeted in clinic to treat patients with Parkinson disease.

Zona fasciculata

A middle region of the adrenal cortex responsible for the production of cortisol in humans and corticosterone in rodents.

Nucleus accumbens

Brain region in the ventral striatum involved in processing of motivation, aversion, reward and learning.

Phonons

Atomic lattice vibration waves carrying thermal energy.

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Romero, G., Park, J., Koehler, F. et al. Modulating cell signalling in vivo with magnetic nanotransducers. Nat Rev Methods Primers 2, 92 (2022). https://doi.org/10.1038/s43586-022-00170-2

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