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

Recently, optical stimulation has begun to unravel the neuronal processing that controls certain animal behaviours. 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.

[1]  K. Kobs,et al.  Rhodamine B and rhodamine 101 as reference substances for fluorescence quantum yield measurements , 1980 .

[2]  C. Kenyon,et al.  The nematode Caenorhabditis elegans. , 1988, Science.

[3]  N. Munakata [Genetics of Caenorhabditis elegans]. , 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[4]  D E Ingber,et al.  Mechanotransduction across the cell surface and through the cytoskeleton. , 1993, Science.

[5]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[6]  Evaluation of temperature increase with different amounts of magnetite in liver tissue samples. , 1997, Investigative radiology.

[7]  A. Basbaum,et al.  The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli , 1998, Neuron.

[8]  N. Wittenburg,et al.  Thermal avoidance in Caenorhabditis elegans: an approach to the study of nociception. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  B. Zemelman,et al.  Selective Photostimulation of Genetically ChARGed Neurons , 2002, Neuron.

[10]  Xunbin Wei,et al.  Selective cell targeting with light-absorbing microparticles and nanoparticles. , 2003, Biophysical journal.

[11]  Anellated Hemicyanine Dyes with Large Symmetrical Solvatochromism of Absorption and Fluorescence , 2003 .

[12]  Shan X. Wang,et al.  Shape-controlled synthesis and shape-induced texture of MnFe2O4 nanoparticles. , 2004, Journal of the American Chemical Society.

[13]  S. Arduini,et al.  Thermophoresis of DNA determined by microfluidic fluorescence , 2004, The European physical journal. E, Soft matter.

[14]  Hao Zeng,et al.  Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. , 2004, Journal of the American Chemical Society.

[15]  E. Isacoff,et al.  Light-activated ion channels for remote control of neuronal firing , 2004, Nature Neuroscience.

[16]  Werner A. Kaiser,et al.  Maghemite nanoparticles with very high AC-losses for application in RF-magnetic hyperthermia , 2004 .

[17]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[18]  Hao Zeng,et al.  Bio-functionalization of monodisperse magnetic nanoparticles and their use as biomolecular labels in a magnetic tunnel junction based sensor. , 2005, The journal of physical chemistry. B.

[19]  M. Howarth,et al.  Targeting quantum dots to surface proteins in living cells with biotin ligase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Jinwoo Cheon,et al.  Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. , 2005, Journal of the American Chemical Society.

[21]  Susana Q. Lima,et al.  Remote Control of Behavior through Genetically Targeted Photostimulation of Neurons , 2005, Cell.

[22]  Wei Zhang,et al.  Thermooptical properties of gold nanoparticles embedded in ice: characterization of heat generation and melting. , 2006, Nano letters.

[23]  Pieter C Dorrestein,et al.  A monovalent streptavidin with a single femtomolar biotin binding site , 2006, Nature Methods.

[24]  Alexander Borst,et al.  A FRET-based calcium biosensor with fast signal kinetics and high fluorescence change. , 2006, Biophysical journal.

[25]  Karsten Weis,et al.  Analysis of a RanGTP-regulated gradient in mitotic somatic cells , 2006, Nature.

[26]  Jinwoo Cheon,et al.  Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging , 2007, Nature Medicine.

[27]  J. Dobson,et al.  Selective activation of mechanosensitive ion channels using magnetic particles , 2007, Journal of The Royal Society Interface.

[28]  M. Howarth,et al.  Imaging proteins in live mammalian cells with biotin ligase and monovalent streptavidin , 2008, Nature Protocols.

[29]  Donald E Ingber,et al.  Nanomagnetic actuation of receptor-mediated signal transduction. , 2008, Nature nanotechnology.

[30]  Jung Soo Suk,et al.  Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that "slip" through the human mucus barrier. , 2008, Angewandte Chemie.

[31]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[32]  K. Deisseroth,et al.  Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning , 2009, Science.