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

Journal name:
Nature Nanotechnology
Year published:
Published online


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.

At a glance


  1. Principles of ion channel stimulation using nanoparticle heating and local temperature sensing.
    Figure 1: Principles of ion channel stimulation using nanoparticle heating and local temperature sensing.

    a, Schematic, drawn to scale, showing local heating of streptavidin–DyLight549 (orange)-coated superparamagnetic nanoparticles (grey) in a RF magnetic field (B ~ ) and heat (red)-induced opening of TRPV1. The AP-CFP-TM protein binds the nanoparticles through the biotinylated AP domain (green box), which is anchored to the membrane by the TM (blue box) and CFP (cyan box) domains. b, Temperature dependence of the fluorescence intensity and lifetime of streptavidin–DyLight549 (ΔF/F = −1.5% °C−1, measured in an externally heated nanoparticle dispersion). c, Applying a RF magnetic field to a nanoparticle dispersion increased the nanoparticle surface temperature (red trace, change in temperature measured by DyLight549 fluorescence) while only moderately changing the solution temperature (green trace, change in temperature measured by YFP fluorescence). Inset shows a schematic of the nanoparticle dispersion (green dots represent YFP; red rings indicate the streptavidin–DyLight549 coating around the nanoparticles (grey)).

  2. Genetic targeting of nanoparticles to specific cells and localized membrane heating.
    Figure 2: Genetic targeting of nanoparticles to specific cells and localized membrane heating.

    a–d, Microscopy images showing a group of HEK 293 cells, two of which are expressing Golgi-targeted GFP and the biotinylated membrane protein AP-CFP-TM (ref. 19). Differential interference contrast (DIC) image displaying all cells (a), green fluorescence image indicating the Golgi localized GFP (b), cyan fluorescence marking the membrane protein AP-CFP-TM (c), red fluorescence of the DyLight549 (d) on the nanoparticles, which are exclusively localized on the plasma membrane of the AP-CFP-TM expressing cells. Scale bar, 20 µm. e, During application of the RF magnetic field (t = 30–45 s as indicated by the hatched box), the local temperature increased at the plasma membrane (red, measured by the change in DyLight549 fluorescence intensity), yet remained constant at the Golgi apparatus (green, measured by fluorescence intensity of Golgi-targeted GFP).

  3. Opening of TRPV1 channels and activation of action potentials.
    Figure 3: Opening of TRPV1 channels and activation of action potentials.

    a, TRPV1 opening and calcium influx in HEK 293 cells as a result of capsaicin stimulation (solid line) or nanoparticle (NP) heating (dashed line). The calcium influx was measured as the Citrine/CFP fluorescence intensity ratio of the calcium indicator TN-XL. Magnetic field stimulation of nanoparticle-coated cells (30 s, 40 MHz, 8.4 G, white box) evoked a similar calcium influx as stimulation with 2 µM capsaicin (5 s, hatched box). b, Action potentials were elicited in nanoparticle-coated, cultured hippocampal neurons, which heterologously expressed TRPV1. The membrane potential was recorded using the voltage-sensitive dye ANNINE6. During application of the RF magnetic field, the intensity of the ANNINE6 fluorescence decreased as the membrane temperature increased from 30 to 43 °C, at which point firing of an action potential was observed. Inset: magnified view of the action potential (arrow).

  4. Remote stimulation of thermal avoidance response in C. elegans.
    Figure 4: Remote stimulation of thermal avoidance response in C. elegans.

    a, Fluorescence image sequence of the head region of a C. elegans worm that has been labelled with fluorescein–PEG-coated nanoparticles and anaesthetized with sodium azide (Supplementary Movie S4). During application of the RF magnetic field between 11 and 28 s (square boxes in movie frames), the fluorescein fluorescence intensity decreased. This decrease corresponds to a temperature increase from 20 to 34 °C (t = 17 s), at which point the worm retracted. b, Plot of the time course of the fluorescence intensity and temperature for the amphid region. c, Bright-field image of the C. elegans worm, indicating the head region shown in the image sequence in a. d, Schematic highlighting the basic structures of the head region, where the dendrites of multiple sensory neurons reach the external environment (via the amphid pore).


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  1. Department of Physics, University at Buffalo, the State University of New York, Buffalo, New York 14260, USA

    • Heng Huang,
    • Savas Delikanli,
    • Hao Zeng &
    • Arnd Pralle
  2. Department of Biological Sciences, University at Buffalo, the State University of New York, Buffalo, New York 14260, USA

    • Denise M. Ferkey


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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