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Chemical amplification of magnetic field effects relevant to avian magnetoreception

Nature Chemistry volume 8, pages 384–391 (2016)Cite this article

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Abstract

Magnetic fields as weak as the Earth's can change the yields of radical pair reactions even though the energies involved are orders of magnitude smaller than the thermal energy, kBT, at room temperature. Proposed as the source of the light-dependent magnetic compass in migratory birds, the radical pair mechanism is thought to operate in cryptochrome flavoproteins in the retina. Here we demonstrate that the primary magnetic field effect on flavin photoreactions can be amplified chemically by slow radical termination reactions under conditions of continuous photoexcitation. The nature and origin of the amplification are revealed by studies of the intermolecular flavin–tryptophan and flavin–ascorbic acid photocycles and the closely related intramolecular flavin–tryptophan radical pair in cryptochrome. Amplification factors of up to 5.6 were observed for magnetic fields weaker than 1 mT. Substantial chemical amplification could have a significant impact on the viability of a cryptochrome-based magnetic compass sensor.

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Figure 1: Intermolecular radical pair reactions of flavins.
Figure 2: Amplified MFEs in intermolecular reactions of flavins.
Figure 3: Characteristics of the amplified MFE.
Figure 4: Amplified MFEs in the low-field region.
Figure 5: Intramolecular radical pair reactions of cryptochromes.
Figure 6: Amplified MFEs in a cryptochrome.
Figure 7: Simulations of changes in radical concentrations induced by a magnetic field.

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References

  1. Wiltschko, R. & Wiltschko, W. Avian magnetic compass: its functional properties and physical basis. Curr. Zool. 56, 265–276 (2010).

    Article  Google Scholar 

  2. Mouritsen, H. in Neurosciences—from Molecule to Behavior: a University Textbook (eds Galizia, C. G. & Lledo, P.-M. ) 427–443 (Springer-Verlag, 2013).

    Book  Google Scholar 

  3. Kishkinev, D. A. & Chernetsov, N. S. Magnetoreception systems in birds: a review of current research. Biol. Bull. Rev. 5, 46–62 (2015).

    Article  Google Scholar 

  4. Ritz, T., Adem, S. & Schulten, K. A model for photoreceptor-based magnetoreception in birds. Biophys. J. 78, 707–718 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rodgers, C. T. & Hore, P. J. Chemical magnetoreception in birds: a radical pair mechanism. Proc. Natl Acad. Sci. USA 106, 353–360 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mouritsen, H. & Hore, P. J. The magnetic retina: light-dependent and trigeminal magnetoreception in migratory birds. Curr. Opin. Neurobiol. 22, 343–352 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Chaves, I. et al. The cryptochromes: blue light photoreceptors in plants and animals. Annu. Rev. Plant Biol. 62, 335–364 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Giovani, B., Byrdin, M., Ahmad, M. & Brettel, K. Light-induced electron transfer in a cryptochrome blue-light photoreceptor. Nature Struct. Biol. 10, 489–490 (2003).

    Article  CAS  PubMed  Google Scholar 

  9. Zeugner, A. et al. Light-induced electron transfer in Arabidopsis cryptochrome-1 correlates with in vivo function. J. Biol. Chem. 280, 19437–19440 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Biskup, T. et al. Direct observation of a photoinduced radical pair in a cryptochrome blue-light photoreceptor. Angew. Chem. Int. Ed. 48, 404–407 (2009).

    Article  CAS  Google Scholar 

  11. Maeda, K. et al. Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor. Proc. Natl Acad. Sci. USA 109, 4774–4779 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Niessner, C. et al. Magnetoreception: activated cryptochrome 1a concurs with magnetic orientation in birds. J. R. Soc. Interface 10, 20130638 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Niessner, C., Denzau, S., Peichl, L., Wiltschko, W. & Wiltschko, R. Magnetoreception in birds: I. Immunohistochemical studies concerning the cryptochrome cycle. J. Exp. Biol. 217, 4221–4224 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lee, A. A. et al. Alternative radical pairs for cryptochrome-based magnetoreception. J. R. Soc. Interface 11, 20131063 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Hogben, H. J., Efimova, O., Wagner-Rundell, N., Timmel, C. R. & Hore, P. J. Possible involvement of superoxide and dioxygen with cryptochrome in avian magnetoreception: origin of Zeeman resonances observed by in vivo EPR spectroscopy. Chem. Phys. Lett. 480, 118–122 (2009).

    Article  CAS  Google Scholar 

  16. Solov'yov, I. A. & Schulten, K. Magnetoreception through cryptochrome may involve superoxide. Biophys. J. 96, 4804–4813 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Conrad, K. S., Manahan, C. C. & Crane, B. R. Photochemistry of flavoprotein light sensors. Nature Chem. Biol. 10, 801–809 (2014).

    Article  CAS  Google Scholar 

  18. Gao, J. et al. Trp triad-dependent rapid photoreduction is not required for the function of Arabidopsis CRY1. Proc. Natl Acad. Sci. USA 112, 9135–9140 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Steiner, U. E. & Ulrich, T. Magnetic field effects in chemical kinetics and related phenomena. Chem. Rev. 89, 51–147 (1989).

    Article  CAS  Google Scholar 

  20. Liedvogel, M. & Mouritsen, H. Cryptochromes—a potential magnetoreceptor: what do we know and what do we want to know? J. R. Soc. Interface 7, S147–S162 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Dodson, C. A., Hore, P. J. & Wallace, M. I. A radical sense of direction: signalling and mechanism in cryptochrome magnetoreception. Trends Biochem. Sci. 38, 435–446 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Mouritsen, H. et al. Cryptochromes and neuronal-activity markers colocalize in the retina of migratory birds during magnetic orientation. Proc. Natl Acad. Sci. USA 101, 14294–14299 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Möller, A., Sagasser, S., Wiltschko, W. & Schierwater, B. Retinal cryptochrome in a migratory passerine bird: a possible transducer for the avian magnetic compass. Naturwissenschaften 91, 585–588 (2004).

    Article  PubMed  CAS  Google Scholar 

  24. Niessner, C. et al. Avian ultraviolet/violet cones identified as probable magnetoreceptors. PLoS ONE 6, e20091 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gegear, R. J., Casselman, A., Waddell, S. & Reppert, S. M. Cryptochrome mediates light-dependent magnetosensitivity in Drosophila. Nature 454, 1014–1018 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yoshii, T., Ahmad, M. & Helfrich-Forster, C. Cryptochrome mediates light-dependent magnetosensitivity of Drosophila’s circadian clock. PLoS Biol. 7, 813–819 (2009).

    Article  CAS  Google Scholar 

  27. Gegear, R. J., Foley, L. E., Casselman, A. & Reppert, S. M. Animal cryptochromes mediate magnetoreception by an unconventional photochemical mechanism. Nature 463, 804–807 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Foley, L. E., Gegear, R. J. & Reppert, S. M. Human cryptochrome exhibits light-dependent magnetosensitivity. Nature Commun. 2, 356 (2011).

    Article  CAS  Google Scholar 

  29. Fedele, G. et al. Genetic analysis of circadian responses to low frequency electromagnetic fields in Drosophila melanogaster. PLoS Genet. 10, e1004804 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Fedele, G., Green, E. W., Rosato, E. & Kyriacou, C. P. An electromagnetic field disrupts negative geotaxis in Drosophila via a CRY-dependent pathway. Nature Commun. 5, 4391 (2014).

    Article  CAS  Google Scholar 

  31. Marley, R., Giachello, C. N. G., Scrutton, N. S., Baines, R. A. & Jones, A. R. Cryptochrome-dependent magnetic field effect on seizure response in Drosophila larvae. Sci. Rep. 4, 5799 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ahmad, M., Galland, P., Ritz, T., Wiltschko, R. & Wiltschko, W. Magnetic intensity affects cryptochrome-dependent responses in Arabidopsis thaliana. Planta 225, 615–624 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Harris, S.-R. et al. Effect of magnetic fields on cryptochrome-dependent responses in Arabidopsis thaliana. J. R. Soc. Interface 6, 1193–1205 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Henbest, K. B. et al. Magnetic-field effect on the photoactivation reaction of Escherichia coli DNA photolyase. Proc. Natl Acad. Sci. USA 105, 14395–14399 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Binhi, V. N. Stochastic dynamics of magnetosomes and a mechanism of biological orientation in the geomagnetic field. Bioelectromagnetics 27, 58–63 (2006).

    Article  CAS  PubMed  Google Scholar 

  36. Winklhofer, M. & Kirschvink, J. L. A quantitative assessment of torque-transducer models for magnetoreception. J. R. Soc. Interface 7, S273–S289 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Cai, J. Quantum probe and design for a chemical compass with magnetic nanostructures. Phys. Rev. Lett. 106, 100501 (2011).

    Article  PubMed  CAS  Google Scholar 

  38. Miura, T., Maeda, K. & Arai, T. Effect of coulomb interaction on the dynamics of the radical pair in the system of flavin mononucleotide and hen egg-white lysozyme (HEWL) studied by a magnetic field effect. J. Phys. Chem. B 107, 6474–6478 (2003).

    Article  CAS  Google Scholar 

  39. Murakami, M., Maeda, K. & Arai, T. Dynamics of intramolecular electron transfer reaction of FAD studied by magnetic field effects on transient absorption spectra. J. Phys. Chem. A 109, 5793–5800 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Neil, S. R. T. et al. Broadband cavity-enhanced detection of magnetic field effects in chemical models of a cryptochrome magnetoreceptor. J. Phys. Chem. B 118, 4177–4184 (2014).

    Article  CAS  PubMed  Google Scholar 

  41. Evans, E. W. et al. Sensitive fluorescence-based detection of magnetic field effects in photoreactions of flavins. Phys. Chem. Chem. Phys. 17, 18456–18463 (2015).

    Article  CAS  PubMed  Google Scholar 

  42. Dodson, C. A. et al. Fluorescence-detected magnetic field effects on radical pair reactions from femtolitre volumes. Chem. Commun. 51, 8023–8026 (2015).

    Article  CAS  Google Scholar 

  43. Beardmore, J. P., Antill, L. M. & Woodward, J. R. Optical absorption and magnetic field effect based imaging of transient radicals. Angew. Chem. 54, 8494–8497 (2015).

    Article  CAS  Google Scholar 

  44. Hore, P. J. & Broadhurst, R. W. Photo-CIDNP of biopolymers. Prog. Nucl. Magn. Reson. Spectrosc. 25, 345–402 (1993).

    Article  CAS  Google Scholar 

  45. Morozova, O. B. et al. Time resolved CIDNP study of electron transfer reactions in proteins and model compounds. Mol. Phys. 100, 1187–1195 (2002).

    Article  CAS  Google Scholar 

  46. Mok, K. H. & Hore, P. J. Photo-CIDNP NMR methods for studying protein folding. Methods 34, 75–87 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Atkins, P. W. & Evans, G. T. Magnetic-field effects on chemiluminescent fluid solutions. Mol. Phys. 29, 921–935 (1975).

    Article  CAS  Google Scholar 

  48. Mani, T. & Vinogradov, S. A. Magnetic field effects on triplet–triplet annihilation in solutions: modulation of visible/NIR luminescence. J. Phys. Chem. Lett. 4, 2799–2804 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hore, P. J. & Kaptein, R. Proton nuclear magnetic-resonance assignments and surface accessibility of tryptophan residues in lysozyme using photochemically induced dynamic nuclear polarization spectroscopy. Biochemistry 22, 1906–1911 (1983).

    Article  CAS  PubMed  Google Scholar 

  50. Vaish, S. P. & Tollin, G. Flash photolysis of flavins. V. Oxidation and disproportionation of flavin radicals. J. Bioenerg. 2, 61–72 (1971).

    Article  CAS  PubMed  Google Scholar 

  51. Massey, V. Activation of molecular-oxygen by flavins and flavoproteins. J. Biol. Chem. 269, 22459–22462 (1994).

    Article  CAS  PubMed  Google Scholar 

  52. Brocklehurst, B. Spin correlation in geminate recombination of radical ions in hydrocarbons. 1. Theory of magnetic-field effect. J. Chem. Soc. Faraday Trans. II 72, 1869–1884 (1976).

    Article  CAS  Google Scholar 

  53. Timmel, C. R., Till, U., Brocklehurst, B., McLauchlan, K. A. & Hore, P. J. Effects of weak magnetic fields on free radical recombination reactions. Mol. Phys. 95, 71–89 (1998).

    Article  CAS  Google Scholar 

  54. Weber, S. et al. Origin of light-induced spin-correlated radical pairs in cryptochrome. J. Phys. Chem. B 114, 14745–14754 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Song, S. H. et al. Absorption and fluorescence spectroscopic characterization of cryptochrome 3 from Arabidopsis thaliana. J. Photochem. Photobiol. B 85, 1–16 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Shirdel, J., Zirak, P., Penzkofer, A., Breitkreuz, H. & Wolf, E. Absorption and fluorescence spectroscopic characterisation of the circadian blue-light photoreceptor cryptochrome from Drosophila melanogaster (dCry). Chem. Phys. 352, 35–47 (2008).

    Article  CAS  Google Scholar 

  57. Weaver, J. C., Vaughan, T. E. & Astumian, R. D. Biological sensing of small field differences by magnetically sensitive chemical reactions. Nature 405, 707–709 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Maeda, K. et al. Following radical pair reactions in solution: a step change in sensitivity using cavity ring-down detection. J. Am. Chem. Soc. 133, 17807–17815 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Rodgers, C. T., Norman, S. A., Henbest, K. B., Timmel, C. R. & Hore, P. J. Determination of radical re-encounter probability distributions from magnetic field effects on reaction yields. J. Am. Chem. Soc. 129, 6746–6755 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Hoang, N. et al. Human and Drosophila cryptochromes are light activated by flavin photoreduction in living cells. PLoS Biol. 6, e160 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Bouly, J. P. et al. Cryptochrome blue light photoreceptors are activated through interconversion of flavin redox states. J. Biol. Chem. 282, 9383–9391 (2007).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank N. Baker for expert technical assistance. E.W.E. is indebted to the Engineering and Physical Sciences Research Council and SABMiller plc for his doctoral scholarship. C.A.D. gratefully acknowledges her current Imperial College Junior Research Fellowship. We are grateful to the following for financial support: the Defense Advanced Research Projects Agency (QuBE: N66001-10-1-4061), the European Research Council (under the European Union's 7th Framework Programme, FP7/2007-2013/ERC grant agreement No. 340451), the Air Force Office of Scientific Research (Air Force Materiel Command, USAF award No. FA9550-14-1-0095) and the EMF Biological Research Trust.

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Author notes

  1. Charlotte A. Dodson

    Present address: Present address: Molecular Medicine, National Heart & Lung Institute, Imperial College London, London SW7 2AZ, UK,

  2. Daniel R. Kattnig and Emrys W. Evans: These authors contributed equally

Authors and Affiliations

  1. Department of Chemistry, University of Oxford, Physical & Theoretical Chemistry Laboratory, Oxford, OX1 3QZ, UK

    Daniel R. Kattnig, Stuart R. Mackenzie & P. J. Hore

  2. Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, Oxford, OX1 3QR, UK

    Emrys W. Evans, Victoire Déjean & Christiane R. Timmel

  3. Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, OX1 3TA, UK

    Charlotte A. Dodson & Mark I. Wallace

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Contributions

D.R.K. and E.W.E. contributed equally to this work. D.R.K., E.W.E. and V.D. designed and performed the experiments. D.R.K. and E.W.E. analysed the data. C.A.D. advised on the production of the AtCry1 samples. M.I.W. helped oversee the fluorescence microscopy experiments. C.R.T., S.R.M. and P.J.H. coordinated the study. P.J.H., D.R.K. and E.W.E. wrote the paper. All the authors discussed the results and commented on the manuscript.

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Correspondence to P. J. Hore.

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Kattnig, D., Evans, E., Déjean, V. et al. Chemical amplification of magnetic field effects relevant to avian magnetoreception. Nature Chem 8, 384–391 (2016). https://doi.org/10.1038/nchem.2447

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