Abstract
The remarkable ability of migratory birds to navigate accurately using the geomagnetic field for journeys of thousands of kilometres is currently thought to arise from radical pair reactions inside a protein called cryptochrome. In this article, we explain the quantum mechanical basis of the radical pair mechanism and why it is currently the dominant theory of compass magnetoreception. We also provide a brief account of two important computational simulation techniques that are used to study the mechanism in cryptochrome: spin dynamics and molecular dynamics. At the end, we provide an overview of current research on quantum mechanical processes in avian cryptochromes and the computational models for describing them.
Zusammenfassung
Zugvögel können mit Hilfe des Erdmagnetfeldes über tausende Kilometer hinweg akkurat navigieren. Es wird heutzutage angenommen, dass quantenmechanische Vorgänge im Cryptochromprotein diese Fähigkeit ermöglichen. Bei diesen Prozessen handelt es sich um Radikalpaar-Reaktionen. In diesem Artikel werden wir den Radikalpaarmechanismus erklären und erläutern, warum er momentan die vorherrschende Theorie ist. Des Weiteren werden wir kurz zwei wichtige, rechnerische Simulationstechniken vorstellen, die benutzt werden um Cryptochrome zu studieren: Spindynamik und Molekulardynamik. Abschließend geben wir einen Überblick über aktuelle Forschungsfragen.
Funding source: H2020 European Research Council
Award Identifier / Grant number: 810002, Synergy Grant, QuantumBirds
Funding source: Volkswagen Foundation
Funding source: Deutsche Forschungsgemeinschaft
Award Identifier / Grant number: 395940726—SFB 1372
Award Identifier / Grant number: RTG 1885
About the authors
Siu Ying Wong completed her MChem Chemistry degree at the University of Oxford. She joined SFB 1372 as a PhD student with the QuantBio group at the University of Oldenburg in 2019, jointly supervised by Prof. Peter Hore (University of Oxford) and QuantBio group leader Prof. Ilia Solov’yov. Her main research focus concerns spin dynamics simulations of radical pairs.
Anders Frederiksen joined the QuantBio group during his bachelor degree in 2017 when it was still located in Denmark. As a member of the group, he acquired his Masters degree in Physics in 2020 at the University of Southern Denmark. After, he moved to the University of Oldenburg in 2020 to continue in the group as a PhD student in SFB 1372. He is supervised by Prof. Ilia Solov’yov and his main research topic focuses on effects of mutations in cryptochrome 4.
Maja Hanić obtained her Chemistry degree at the University of Zagreb. She joined RTG 1885 as a PhD student with the QuantBio group at the University of Oldenburg in 2020 and is supervised by Prof. Ilia Solov’yov. Her research focuses on structural traits of avian cryptochrome 4.
Fabian Schuhmann got his Masters degree in Mathematics at the Ruhr-Universität Bochum and then joined the QuantBio group in Oldenburg as a PhD student. He is part of RTG 1885 “Molecular Basis of Sensory Biology” and is supervised by Prof. Ilia Solov’yov. His research focuses on theoretical and computational methods for sensory biology.
Gesa Grüning received her Masters degree in Physics at the University of Heidelberg and joined the QuantBio group in Oldenburg as a PhD student in 2020. She is part of SFB 1372 and RTG 1885. Her supervisor is Prof. Ilia Solov’yov and her research focus is spin relaxation in cryptochromes.
P. J. Hore has spent most of his life in the Department of Chemistry at the University of Oxford, first as a student and then, after a two-year postdoc at the University of Groningen (1980–82), as a Junior Research Fellow (1982–83). He is now Professor of Chemistry and a Fellow and Tutor of Corpus Christi College. His work on magnetoreception mechanisms is funded in part by an ERC Synergy Grant, QuantumBirds, held jointly with Prof. Henrik Mouritsen (University of Oldenburg). He holds a Mercator Fellowship within SFB 1372.
Ilia A. Solov’yov obtained his Ph.D. with Summa cum Laude from the Goethe University (Frankfurt am Main, Germany) in 2008. In 2009 Solov’yov received a second doctoral degree in theoretical physics from the Ioffe Physical-Technical Institute (St. Petersburg, Russia). After two post-doctoral appointments (Goethe University and University of Illinois at Urbana-Champaign, USA) Solov’yov joined in 2013 the Faculty of Sciences at the University of Southern Denmark as an Assistant Professor. He was promoted to a permanent position in 2014 and established the QuantBio group. In 2019, Solov’yov became a VW Lichtenberg Professor and relocated his research group to Oldenburg, Germany. Solov’yov’s current research interests cover a broad range of questions on theory of biomolecules and smart inorganic materials.
Acknowledgements
The authors are grateful to the following for providing drawings used in Figure 1: Corinna Langebrake for the European robin and Domagoj Ciglar for the bird’s eye.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: The authors gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (Project Nos. 395940726—SFB 1372 ‘Magnetoreception and Navigation in Vertebrates’ and GRK1885), the European Research Council (under the European Union’s Horizon 2020 research and innovation programme, Grant Agreement No. 810002, Synergy Grant, QuantumBirds) and the Volkswagen Foundation.
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Conflict of interest statement: The authors declare no conflicts of interest.
References
Ahmad, M. and Cashmore, R.A. (1993). HY4 gene of A. thaliana encodes a protein with characteristics of a blue-light photoreceptor. Nature 366, 162–166, https://doi.org/10.1038/366162a0.Search in Google Scholar PubMed
Bartölke, R., Behrmann, H., Görtemaker, K., Yee, C., Xu, J., Behrmann, E., and Koch, K.-W. (2021). The secrets of cryptochromes: photoreceptors, clock proteins, and magnetic sensors. Neuroforum 27, 151–157.10.1515/nf-2021-0006Search in Google Scholar
Einwich, A., Dedek, K., Seth, P.K., Laubinger, S., and Mouritsen, H. (2020). A novel isoform of cryptochrome 4 (Cry4b) is expressed in the retina of a night-migratory songbird. Sci. Rep. 4, 15794, https://doi.org/10.1038/s41598-020-72579-2.Search in Google Scholar PubMed PubMed Central
Engels, S., Schneider, N.L., Lefeldt, N., Hein, C.M., Zapka, M., Michalik, A., Elbers, D., Kittel, A., Hore, P.J., and Mouritsen, H. (2014). Anthropogenic electromagnetic noise disrupts magnetic compass orientation in a migratory bird. Nature 509, 353–356, https://doi.org/10.1038/nature13290.Search in Google Scholar PubMed
Fay, T.P., Lindoy, L.P., Manolopoulos, D.E., and Hore, P.J. (2020). How quantum is radical pair magnetoreception? Faraday Discuss 221, 77–91, https://doi.org/10.1039/c9fd00049f.Search in Google Scholar PubMed
Günther, A., Einwich, A., Sjulstok, E., Feederle, R., Bolte, P., Koch, K.-W., Solov’yov, I.A., and Mouritsen, H. (2018). Double-cone localization and seasonal expression pattern suggest a role in magnetoreception for European robin cryptochrome 4. Curr. Biol. 28, 211–223, https://doi.org/10.1016/j.cub.2017.12.003.Search in Google Scholar PubMed
Haase, K., Musielak, I., and Heyers, D. (2021). The neuronal correlates of the avian magnetic senses. Neuroforum 27, 167–174.10.1515/nf-2021-0008Search in Google Scholar
Hiscock, H.G., Mouritsen, H., Manolopoulos, D.E., and Hore, P.J. (2017). Disruption of magnetic compass orientation in migratory birds by radiofrequency electromagnetic fields. Biophys. J. 113, 1475–1484, https://doi.org/10.1016/j.bpj.2017.07.031.Search in Google Scholar PubMed PubMed Central
Hiscock, H.G., Worster, S., Kattnig, D.R., Steers, C., Jin, Y., Manolopoulos, D.E., Mouritsen, H., and Hore, P.J. (2016). The quantum needle of the avian magnetic compass. Proc. Natl. Acad. Sci. U. S. A. 113, 4634–4639, https://doi.org/10.1073/pnas.1600341113.Search in Google Scholar PubMed PubMed Central
Hochstoeger, T., Al Said, T., Maestre, D., Walter, F., Vilceanu, A., Pedron, M., Cushion, T.D., Snider, W., Nimpf, S., Nordmann, G.C., et al.. (2020). The biophysical, molecular, and anatomical landscape of pigeon CRY4: A candidate light-based quantal magnetosensor. Sci. Adv. 6, eabb9110, https://doi.org/10.1126/sciadv.abb9110.Search in Google Scholar PubMed PubMed Central
Hogben, H.J., Efimova, O., Wagner-Rundell, N., Timmel, C.R., and Hore, P.J. (2009). 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, https://doi.org/10.1016/j.cplett.2009.08.051.Search in Google Scholar
Hogben, H.J., Krzystyniak, M., Charnock, G.T.P., Hore, P.J., and Kuprov, I. (2011). Spinach – A software library for simulation of spin dynamics in large spin systems. J. Magn. Reson. 208, 179–194, https://doi.org/10.1016/j.jmr.2010.11.008.Search in Google Scholar PubMed
Hore, P.J. and Mouritsen, H. (2016). The radical-pair mechanism of magnetoreception. Annu. Rev. Biophys. 45, 299–344, https://doi.org/10.1146/annurev-biophys-032116-094545.Search in Google Scholar PubMed
Humphrey, W., Dalke, A., and Schulten, K. (1996). VMD: Visual molecular dynamics. J. Mol. Graph. 14, 33–38, https://doi.org/10.1016/0263-7855(96)00018-5.Search in Google Scholar PubMed
Kattnig, D.R., Nielsen, C., and Solov’yov, I.A. (2018). Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4. New J. Phys. 20, 083018, https://doi.org/10.1088/1367-2630/aad70f.Search in Google Scholar
Kattnig, D.R., Solov’yov, I.A., and Hore, P.J. (2016a). Electron spin relaxation in cryptochrome-based magnetoreception. Phys. Chem. Chem. Phys. 18, 12443–12456, https://doi.org/10.1039/c5cp06731f.Search in Google Scholar PubMed
Kattnig, D.R., Sowa, J.K., Solov’yov, I.A., and Hore, P.J. (2016b). Electron spin relaxation can enhance the performance of a cryptochrome-based magnetic compass sensor. New J. Phys. 18, 63007, https://doi.org/10.1088/1367-2630/18/6/063007.Search in Google Scholar
Kobylkov, D., Wynn, J., Winklhofer, M., Chetverikova, R., Xu, J., Hiscock, H., Hore, P.J., and Mouritsen, H. (2019). Electromagnetic 0.1–100 kHz noise does not disrupt orientation in a night-migrating songbird implying a spin coherence lifetime of less than 10 µs. J. R. Soc. Interface 16, 20190716, https://doi.org/10.1098/rsif.2019.0716.Search in Google Scholar PubMed PubMed Central
Korol, V., Husen, P., Sjulstok, E., Nielsen, C., Friis, I., Frederiksen, A., Salo, A.B., and Solov’yov, I.A. (2020). Introducing VIKING: A novel online platform for multiscale modeling. ACS Omega 5, 1254–1260, https://doi.org/10.1021/acsomega.9b03802.Search in Google Scholar PubMed PubMed Central
Lau, J.C.S., Wagner-Rundell, N., Rodgers, C.T., Green, N.J.B., and Hore, P.J. (2010). Effects of disorder and motion in a radical pair magnetoreceptor. J. Roy. Soc. Interface 7, S257–S264, https://doi.org/10.1098/rsif.2009.0399.focus.Search in Google Scholar PubMed PubMed Central
Lee, A.A., Lau, J.C.S., Hogben, H.J., Biskup, T., Kattnig, D.R., and Hore, P.J. (2014). Alternative radical pairs for cryptochrome-based magnetoreception. J. R. Soc. Interface 11, 20131063, https://doi.org/10.1098/rsif.2013.1063.Search in Google Scholar PubMed PubMed Central
Lewis, A.M., Manolopoulos, D.E., and Hore, P.J. (2014). Asymmetric recombination and electron spin relaxation in the semiclassical theory of radical pair reactions. J. Chem. Phys. 141, 44111, https://doi.org/10.1063/1.4890659.Search in Google Scholar PubMed
Maeda, K., Neil, S.R.T., Henbest, K.B., Weber, S., Schleicher, E., Hore, P.J., Mackenzie, S.R., and Timmel, C.R. (2011). Following radical pair reactions in solution: A step change in sensitivity using cavity ring-down detection. J. Am. Chem. Soc. 133, 17807–17815, https://doi.org/10.1021/ja206783t.Search in Google Scholar PubMed
Maeda, K., Robinson, A.J., Henbest, K.B., Hogben, H.J., Biskup, T., Ahmad, M., Schleicher, E., Weber, S., Timmel, C.R., and Hore, P.J. (2012). Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor. Proc. Natl. Acad. Sci. U. S. A. 109, 4774–4779, https://doi.org/10.1073/pnas.1118959109.Search in Google Scholar PubMed PubMed Central
Manolopoulos, D.E. and Hore, P.J. (2013). An improved semiclassical theory of radical pair recombination reactions. J. Chem. Phys. 139, 124106, https://doi.org/10.1063/1.4821817.Search in Google Scholar PubMed
Mouritsen, H. (2018). Long-distance navigation and magnetoreception in migratory animals. Nature 558, 50–59, https://doi.org/10.1038/s41586-018-0176-1.Search in Google Scholar PubMed
Mouritsen, H., Feenders, G., Liedvogel, M., Wada, K., and Jarvis, E.D. (2005). Night-vision brain area in migratory songbirds. Proc. Natl. Acad. Sci. U.S.A. 102, 8339–8344, https://doi.org/10.1073/pnas.0409575102.Search in Google Scholar PubMed PubMed Central
Müller, P., Yamamoto, J., Martin, R., Iwai, S., and Brettel, K. (2015). Discovery and functional analysis of a 4th electron-transferring tryptophan conserved exclusively in animal cryptochromes and (6-4) photolyases. Chem. Commun. 51, 15502–15505, https://doi.org/10.1039/c5cc06276d.Search in Google Scholar PubMed
Neil, S.R.T., Li, J., Sheppard, D.M.W., Storey, J., Maeda, K., Henbest, K.B., Hore, P.J., Timmel, C.R., and Mackenzie, S.R. (2014). Broadband cavity-enhanced detection of magnetic field effects in chemical models of a cryptochrome magnetoreceptor. J. Phys. Chem. B 118, 4177–4184, https://doi.org/10.1021/jp500732u.Search in Google Scholar PubMed
Nielsen, C., Kattnig, D.R., Sjulstok, E., Hore, P.J., and Solov’yov, I.A. (2017). Ascorbic acid may not be involved in cryptochrome-based magnetoreception. J. R. Soc. Interface 14, 20170657, https://doi.org/10.1098/rsif.2017.0657.Search in Google Scholar PubMed PubMed Central
Nielsen, C. and Solov’yov, I.A. (2019). MolSpin—Flexible and extensible general spin dynamics software. J. Chem. Phys. 151, 194105, https://doi.org/10.1063/1.5125043.Search in Google Scholar PubMed
Phillips, J.C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R.D., Kale, L., and Schulten, K. (2005). Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781–1802, https://doi.org/10.1002/jcc.20289.Search in Google Scholar PubMed PubMed Central
Phillips, J.C., Hardy, D.J., Maia, J.D.C., Stone, J.E., Ribeiro, J.V., Bernardi, R.C., Buch, R., Fiorin, G., Hénin, J., Jiang, W., et al.. (2020). Scalable molecular dynamics on CPU and GPU architectures with NAMD. J. Chem. Phys. 153, 44130, https://doi.org/10.1063/5.0014475.Search in Google Scholar PubMed PubMed Central
Player, T.C. and Hore, P.J. (2019). Viability of superoxide-containing radical pairs as magnetoreceptors. J. Chem. Phys. 151, 225101. https://doi.org/10.1063/1.5129608.Search in Google Scholar PubMed
Ren, Y., Hiscock, H.G., and Hore, P.J. (2021). Angular precision of radical pair compass magnetoreceptors. Biophys. J. 120, 547–555, https://doi.org/10.1016/j.bpj.2020.12.023.Search in Google Scholar PubMed PubMed Central
Ritz, T., Adem, S., and Schulten, K. (2000). A model for photoreceptor-based magnetoreception in birds. Biophys. J. 78, 707–718, https://doi.org/10.1016/s0006-3495(00)76629-x.Search in Google Scholar
Ritz, T., Thalau, P., Phillips, J.B., Wiltschko, R., and Wiltschko, W. (2004). Resonance effects indicate a radical-pair mechanism for avian magnetic compass. Nature 429, 177–180, https://doi.org/10.1038/nature02534.Search in Google Scholar PubMed
Ritz, T., Wiltschko, R., Hore, P.J., Rodgers, C.T., Stapput, K., Thalau, P., Timmel, C.R., and Wiltschko, W. (2009). Magnetic compass of birds is based on a molecule with optimal directional sensitivity. Biophys. J. 96, 3451–3457, https://doi.org/10.1016/j.bpj.2008.11.072.Search in Google Scholar PubMed PubMed Central
Rodgers, C.T. and Hore, P.J. (2009). Chemical magnetoreception in birds: A radical pair mechanism. Proc. Natl. Acad. Sci. U.S.A. 106, 353–360, https://doi.org/10.1073/pnas.0711968106.Search in Google Scholar PubMed PubMed Central
Schuhmann, F., Korol, V., and Solov’yov, I.A. (2021). Introducing Pep McConst—A user-friendly peptide modeler for biophysical applications. J. Comput. Chem. 42, 572–580, https://doi.org/10.1002/jcc.26479.Search in Google Scholar PubMed
Schwarze, S., Schneider, N.-L., Reichl, T., Dreyer, D., Lefeldt, N., Engels, S., Baker, N., Hore, P.J., and Mouritsen, H. (2016). Weak broadband electromagnetic fields are more disruptive to magnetic compass orientation in a night-migratory songbird (Erithacus rubecula) than strong narrow-band fields. Front. Behav. Neurosci. 10, 55, https://doi.org/10.3389/fnbeh.2016.00055.Search in Google Scholar PubMed PubMed Central
Sheppard, D.M.W., Li, J., Henbest, K.B., Neil, S.R.T., Maeda, K., Storey, J., Schleicher, E., Biskup, T., Rodriguez, R., Weber, S., et al.. (2017). Millitesla magnetic field effects on the photocycle of an animal cryptochrome. Sci. Rep. 7, 1–7, https://doi.org/10.1038/srep42228.Search in Google Scholar PubMed PubMed Central
Spiecker, L., Leberecht, B., Langebrake, C., Laurien, M., Apte, S.R., Mouritsen, H., Gerlach, G., and Liedvogel, M. (2021). Endless skies and open seas – how birds and fish navigate. Neuroforum 27, 127–139.10.1515/nf-2021-0009Search in Google Scholar
Steiner, U.E. and Ulrich, T. (1989). Magnetic field effects in chemical kinetics and related phenomena. Chem. Rev. 89, 51–147, https://doi.org/10.1021/cr00091a003.Search in Google Scholar
Wiltschko, R., Stapput, K., Thalau, P., and Wiltschko, W. (2010). Directional orientation of birds by the magnetic field under different light conditions. J. R. Soc. Interface 7, S163–S177, https://doi.org/10.1098/rsif.2009.0367.focus.Search in Google Scholar PubMed PubMed Central
Wiltschko, R. and Wiltschko, W. (1995). Magnetic Orientation in Animals (Berlin: Springer-Verlag).10.1007/978-3-642-79749-1Search in Google Scholar
Wiltschko, W. and Wiltschko, R. (1972). Magnetic compass of European robins. Science 176, 62–64, https://doi.org/10.1126/science.176.4030.62.Search in Google Scholar PubMed
Winklhofer, M. (2010). Magnetoreception. J. Roy. Soc. Interface 7, S131–S134, https://doi.org/10.1098/rsif.2010.0010.focus.Search in Google Scholar PubMed PubMed Central
Wong, S.Y., Solov’yov, I.A., Hore, P.J., and Kattnig, D.R. (2021). Nuclear polarization effects in cryptochrome-based magnetoreception. J. Chem. Phys. 154, 035102, https://doi.org/10.1063/5.0038947.Search in Google Scholar PubMed
Woodward, J.R. (2002). Radical pairs in solution. Prog. React. Kinet. Mech. 27, 165–207, https://doi.org/10.3184/007967402103165388.Search in Google Scholar
Worster, S.B. and Hore, P.J. (2018). Proposal to use superparamagnetic nanoparticles to test the role of cryptochrome in magnetoreception. J. R. Soc. Interface 15, 20180587, https://doi.org/10.1098/rsif.2018.0587.Search in Google Scholar PubMed PubMed Central
Xu, J., Jarocha, L.E., Zollitsch, T., Konowalczyk, M., Henbest, K.B., Richert, S., Golesworthy, M.J., Schmidt, J., Déjean, V., Sowood, D.J.C., et al.. (2021). Magnetic sensitivity of cryptochrome 4 from a migratory songbird. Nature, 594, 535–540.10.1038/s41586-021-03618-9Search in Google Scholar PubMed
Yu, X., Liu, H., Klejnot, J., and Lin, C. (2010). The cryptochrome blue light receptors. Arabidopsis Book, 2010, e0135, https://doi.org/10.1199/tab.0135.Search in Google Scholar PubMed PubMed Central
Zapka, M., Heyers, D., Hein, C.M., Engels, S., Schneider, N.L., Hans, J., Weiler, S., Dreyer, D., Kishkinev, D., Wild, J.M., et al.. (2009). Visual but not trigeminal mediation of magnetic compass information in a migratory bird. Nature 461, 1274–1278, https://doi.org/10.1038/nature08528.Search in Google Scholar PubMed
Zoltowski, B.D., Chelliah, Y., Wickramaratne, A., Jarocha, L., Karki, N., Xu, W., Mouritsen, H., Hore, P.J., Hibbs, R.E., Green, C.B., et al.. (2019). Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon. Proc. Natl. Acad. Sci. U.S.A. 116, 19449–19457, https://doi.org/10.1073/pnas.1907875116.Search in Google Scholar PubMed PubMed Central
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