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Remote control of ion channels and neurons through magnetic-field heating of nanoparticles

Abstract

Recently, optical stimulation1,2,3 has begun to unravel the neuronal processing that controls certain animal behaviours4,5. However, optical approaches are limited by the inability of visible light to penetrate deep into tissues. Here, we show an approach based on radio-frequency magnetic-field heating of nanoparticles to remotely activate temperature-sensitive cation channels in cells. Superparamagnetic ferrite nanoparticles were targeted to specific proteins on the plasma membrane of cells expressing TRPV1, and heated by a radio-frequency magnetic field. Using fluorophores as molecular thermometers, we show that the induced temperature increase is highly localized. Thermal activation of the channels triggers action potentials in cultured neurons without observable toxic effects. This approach can be adapted to stimulate other cell types and, moreover, may be used to remotely manipulate other cellular machinery for novel therapeutics.

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Figure 1: Principles of ion channel stimulation using nanoparticle heating and local temperature sensing.
Figure 2: Genetic targeting of nanoparticles to specific cells and localized membrane heating.
Figure 3: Opening of TRPV1 channels and activation of action potentials.
Figure 4: Remote stimulation of thermal avoidance response in C. elegans.

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Acknowledgements

The authors thank F. Qin for the TRPV1 plasmid and initial assistance, A. Ting for the biotin acceptor peptide-cyan fluorescent protein-transmembrane (AP-CFP-TM) and BirA constructs, and O. Griesbeck for the TN-XL plasmid. J. Pazik is acknowledged for technical assistance, and Y. Hsu, V. Rana, M.J. Ezak and M. Zugravu for valuable discussions.

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A.P. designed the study. H.H. carried out nanoparticle coating and cellular measurements. S.D. and H.Z. were responsible for nanoparticle synthesis and characterization, and D.M.F. for the C. elegans experiments. A.P. and H.H. wrote the manuscript. All authors discussed the results and commented on the manuscript. The work was supported by NSF DMR-0547036, UB IRDF, RF and INSIF.

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Correspondence to Arnd Pralle.

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The authors declare no competing financial interests.

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Huang, H., Delikanli, S., Zeng, H. et al. Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nature Nanotech 5, 602–606 (2010). https://doi.org/10.1038/nnano.2010.125

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