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Chiral phonons in microcrystals and nanofibrils of biomolecules

Nature Photonics volume 16, pages 366–373 (2022)Cite this article

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Abstract

Chiral phonons are concerted mirror-symmetric movements of atomic groups connected by covalent and intermolecular bonds. Such lattice vibrations in crystals of biomolecules should be highly specific to their short- and long-range organizations, but their chiroptical signatures and structure–property relationships remain uncertain. Here we show that terahertz chiroptical spectroscopy enables the registration and attribution of chiral phonons for microscale and nanoscale crystals of amino acids and peptides. Theoretical analysis and computer simulations indicate that sharp mirror-symmetric bands observed for left- and right-handed enantiomers originate from the collective vibrations of biomolecules interconnected by hydrogen bonds into helical chains. The sensitivity of chiral phonons to minute structural changes can be used to identify physical and chemical differences in seemingly identical formulations of dipeptides used in health supplements. The generality of these findings is demonstrated by chiral phonons observed for amyloid nanofibrils of insulin. Their spectral signatures and polarization rotation strongly depend on their maturation stage, which opens a new door for medical applications of terahertz photonics.

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Fig. 1: Hyperspectral THz-TDP setup for the observation of chiral phonons in AA microcrystals.
Fig. 2: Analysis of TA spectra for l- and d-enantiomers of 20 AAs.
Fig. 3: Analysis of TCD and TORD spectra for l- and d-enantiomers of 20 AAs.
Fig. 4: Temperature dependence of TA and TCD spectra for l- and d-glutamine.
Fig. 5: Chiral phonons in CYS and CAR.
Fig. 6: Formation of amyloid fibrils of insulin and their TA and TCD spectra.

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Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding authors upon reasonable request.

Code availability

The analysis codes that support the findings of this study are available from the corresponding authors upon reasonable request.

References

  1. Zhu, H. et al. Observation of chiral phonons. Science 359, 579–582 (2018).

    Article  MathSciNet  ADS  Google Scholar 

  2. Yuan, X. et al. The discovery of dynamic chiral anomaly in a Weyl semimetal NbAs. Nat. Commun. 11, 1259 (2020).

    Article  ADS  Google Scholar 

  3. Yeom, J. et al. Chiromagnetic nanoparticles and gels. Science 359, 309–314 (2018).

    Article  ADS  Google Scholar 

  4. Kurouski, D. Advances of vibrational circular dichroism (VCD) in bioanalytical chemistry. A review. Anal. Chim. Acta 990, 54–66 (2017).

    Article  Google Scholar 

  5. Keiderling, T. A. Protein and peptide secondary structure and conformational determination with vibrational circular dichroism. Curr. Opin. Chem. Biol. 6, 682–688 (2002).

    Article  Google Scholar 

  6. Chen, H., Wu, W., Zhu, J., Yang, S. A. & Zhang, L. Propagating chiral phonons in three-dimensional materials. Nano Lett. 21, 3060–3065 (2021).

    Article  ADS  Google Scholar 

  7. Adu, K. W., Gutiérrez, H. R., Kim, U. J., Sumanasekera, G. U. & Eklund, P. C. Confined phonons in Si nanowires. Nano Lett. 5, 409–414 (2005).

    Article  ADS  Google Scholar 

  8. Markelz, A. G., Roitberg, A. & Heilweil, E. J. Pulsed terahertz spectroscopy of DNA, bovine serum albumin and collagen between 0.1 and 2.0 THz. Chem. Phys. Lett. 320, 42–48 (2000).

    Article  ADS  Google Scholar 

  9. Markelz, A., Whitmire, S., Hillebrecht, J. & Birge, R. THz time domain spectroscopy of biomolecular conformational modes. Phys. Med. Biol. 47, 3797–3805 (2002).

    Article  Google Scholar 

  10. Walther, M., Plochocka, P., Fischer, B., Helm, H. & Uhd Jepsen, P. Collective vibrational modes in biological molecules investigated by terahertz time-domain spectroscopy. Biopolymers 67, 310–313 (2002).

    Article  Google Scholar 

  11. Fischer, B., Walther, M. & Jepsen, P. U. Far-infrared spectroscopy of hydrogen bonding in nucleobases, nucleosides, and nucleotides. In Proc. IEEE Tenth International Conference on Terahertz Electronics 74–76 (IEEE, 2002).

  12. Walther, M., Fischer, B. M. & Jepsen, P. U. Noncovalent intermolecular forces in polycrystalline and amorphous saccharides in the far infrared. Chem. Phys. 288, 261–268 (2003).

    Article  Google Scholar 

  13. Williams, M. R. C., Aschaffenburg, D. J., Ofori-Okai, B. K. & Schmuttenmaer, C. A. Intermolecular vibrations in hydrophobic amino acid crystals: experiments and calculations. J. Phys. Chem. B 117, 10444–10461 (2013).

    Article  Google Scholar 

  14. Rungsawang, R., Ueno, Y., Tomita, I. & Ajito, K. Angle-dependent terahertz time-domain spectroscopy of amino acid single crystals. J. Phys. Chem. B 110, 21259–21263 (2006).

    Article  Google Scholar 

  15. Neu, J. et al. Terahertz spectroscopy of tetrameric peptides. J. Phys. Chem. Lett. 10, 2624–2628 (2019).

    Article  Google Scholar 

  16. Korter, T. M. et al. Terahertz spectroscopy of solid serine and cysteine. Chem. Phys. Lett. 418, 65–70 (2006).

    Article  ADS  Google Scholar 

  17. Singh, R., George, D. K., Benedict, J. B., Korter, T. M. & Markelz, A. G. Improved mode assignment for molecular crystals through anisotropic terahertz spectroscopy. J. Phys. Chem. A 116, 10359–10364 (2012).

    Article  Google Scholar 

  18. Korter, T. M. & Plusquellic, D. F. Continuous-wave terahertz spectroscopy of biotin: vibrational anharmonicity in the far-infrared. Chem. Phys. Lett. 385, 45–51 (2004).

    Article  ADS  Google Scholar 

  19. Day, G. M., Zeitler, J. A., Jones, W., Rades, T. & Taday, P. F. Understanding the influence of polymorphism on phonon spectra: lattice dynamics calculations and terahertz spectroscopy of carbamazepine. J. Phys. Chem. B 110, 447–456 (2006).

    Article  Google Scholar 

  20. Williams, M. R. C. et al. Terahertz spectroscopy of enantiopure and racemic polycrystalline valine. Phys. Chem. Chem. Phys. 13, 11719–11730 (2011).

    Article  Google Scholar 

  21. Choi, W. J. et al. Terahertz circular dichroism spectroscopy of biomaterials enabled by kirigami polarization modulators. Nat. Mater. 18, 820–826 (2019).

  22. Dhillon, S. S. et al. The 2017 terahertz science and technology roadmap. J. Phys. D 50, 043001 (2017).

    Article  ADS  Google Scholar 

  23. Hu, M. et al. Terahertz, infrared and Raman absorption spectra of tyrosine enantiomers and racemic compound. Spectrochim. Acta A 254, 119611 (2021).

    Article  Google Scholar 

  24. Liu, Y., Zhou, T. & Cao, J.-C. Terahertz spectral of enantiomers and racemic amino acids by time-domain-spectroscopy technology. Infrared Phys. Technol. 96, 17–21 (2019).

    Article  ADS  Google Scholar 

  25. True, A. B., Schroeck, K., French, T. A. & Schmuttenmaer, C. A. Terahertz spectroscopy of histidine enantiomers and polymorphs. J. Infrared Milli. Terahz. Waves 32, 691–698 (2011).

    Article  Google Scholar 

  26. Shen, Y.-C. Terahertz pulsed spectroscopy and imaging for pharmaceutical applications: a review. Int. J. Pharm. 417, 48–60 (2011).

    Article  Google Scholar 

  27. Zeitler, J. A. et al. Terahertz pulsed spectroscopy and imaging in pharmaceutical setting—a review. J. Pharm. Pharmacol. 59, 209–223 (2007).

    Article  Google Scholar 

  28. Woutersen, S. et al. Peptide conformational heterogeneity revealed from nonlinear vibrational spectroscopy and molecular-dynamics simulations. J. Chem. Phys. 117, 6833–6840 (2002).

    Article  ADS  Google Scholar 

  29. Rahman, A., Rahman, A. K. & Rao, B. Early detection of skin cancer via terahertz spectral profiling and 3D imaging. Biosens. Bioelectron. 82, 64–70 (2016).

    Article  Google Scholar 

  30. Fitzgerald, A. J. et al. An introduction to medical imaging with coherent terahertz frequency radiation. Phys. Med. Biol. 47, R67 (2002).

  31. Jeong, H. H. et al. Dispersion and shape engineered plasmonic nanosensors. Nat. Commun. 7, 11331 (2016).

  32. Grimme, S., Bannwarth, C. & Shushkov, P. A robust and accurate tight-binding quantum chemical method for structures, vibrational frequencies, and noncovalent interactions of large molecular systems parametrized for all spd-block elements (Z = 1–86). J. Chem. Theory Comput. 13, 1989–2009 (2017).

    Article  Google Scholar 

  33. Kim, Y. et al. Reconfigurable chiroptical nanocomposites with chirality transfer from the macro- to the nanoscale. Nat. Mater. 15, 461–468 (2016).

    Article  ADS  Google Scholar 

  34. Provenzano, C., Pagliusi, P., Mazzulla, A. & Cipparrone, G. Method for artifact-free circular dichroism measurements based on polarization grating. Opt. Lett. 35, 1822–1824 (2010).

    Article  Google Scholar 

  35. Ruggiero, M. T., Sibik, J., Orlando, R., Zeitler, J. A. & Korter, T. M. Measuring the elasticity of poly-l-proline helices with terahertz spectroscopy. Angew. Chem. Int. Ed. 55, 6877–6881 (2016).

    Article  Google Scholar 

  36. Wukovitz, S. W. & Yeates, T. Why protein crystals favour some space-groups over others. Nat. Struct. Biol. 2, 1062–1067 (1995).

    Article  Google Scholar 

  37. Jepsen, P. U. & Fischer, B. M. Dynamic range in terahertz time-domain transmission and reflection spectroscopy. Opt. Lett. 30, 29–31 (2005).

    Article  Google Scholar 

  38. Yin, X., Schäferling, M., Metzger, B. & Giessen, H. Interpreting chiral nanophotonic spectra: the plasmonic Born–Kuhn model. Nano Lett. 13, 6238–6243 (2013).

    Article  ADS  Google Scholar 

  39. Sala, J., Guàrdia, E. & Masia, M. The polarizable point dipoles method with electrostatic damping: implementation on a model system. J. Chem. Phys. 133, 234101 (2010).

    Article  ADS  Google Scholar 

  40. Dos Santos, L. H. R., Krawczuk, A. & Macchi, P. Distributed atomic polarizabilities of amino acids and their hydrogen-bonded aggregates. J. Phys. Chem. A 119, 3285–3298 (2015).

    Article  Google Scholar 

  41. Kühne, T. D. et al. CP2K: an electronic structure and molecular dynamics software package—Quickstep: efficient and accurate electronic structure calculations. J. Chem. Phys. 152, 194103 (2020).

  42. Davies, C. L., Patel, J. B., Xia, C. Q., Herz, L. M. & Johnston, M. B. Temperature-dependent refractive index of quartz at terahertz frequencies. J. Infrared Milli. Terahz. Waves 39, 1236–1248 (2018).

    Article  Google Scholar 

  43. Xie, L. et al. Temperature-dependent terahertz vibrational spectra of tetracycline and its degradation products. Spectrochim. Acta A 222, 117179 (2019).

    Article  Google Scholar 

  44. Altfeder, I. et al. Scanning tunneling microscopy observation of phonon condensate. Sci. Rep. 7, 43214 (2017).

    Article  ADS  Google Scholar 

  45. Lundholm, I. V. et al. Terahertz radiation induces non-thermal structural changes associated with Fröhlich condensation in a protein crystal. Struct. Dyn. 2, 054702 (2015).

    Article  Google Scholar 

  46. Rimer, J. D. et al. Crystal growth inhibitors for the stones through molecular design. Science 330, 337–341 (2010).

    Article  ADS  Google Scholar 

  47. Kawase, M. et al. Application of terahertz absorption spectroscopy to evaluation of aging variation of medicine. Anal. Sci. 27, 209–212 (2011).

    Article  Google Scholar 

  48. Ow, S. Y. & Dunstan, D. E. A brief overview of amyloids and Alzheimer’s disease. Protein Sci. 23, 1315–1331 (2014).

    Article  Google Scholar 

  49. Ivanova, M. I., Sievers, S. A., Sawaya, M. R., Wall, J. S. & Eisenberg, D. Molecular basis for insulin fibril assembly. Proc. Natl Acad. Sci. USA 106, 18990–18995 (2009).

    Article  ADS  Google Scholar 

  50. Jiménez, J. L. et al. The protofilament structure of insulin amyloid fibrils. Proc. Natl Acad. Sci. USA 99, 9196–9201 (2002).

    Article  ADS  Google Scholar 

Download references

Acknowledgements

This work was supported by Vannevar Bush DoD Fellowship to N.A.K. titled ‘Engineered Chiral Ceramics’ ONR N000141812876, ONR COVID-19 Newton Award ‘Pathways to Complexity with “Imperfect” Nanoparticles’ HQ00342010033. This study was also supported in part by the US Defense Advanced Research Projects Agency (DARPA) RadioBio programme under contract HR00111720067, by the Office of Naval Research (MURI N00014-20-1-2479) and by AFOSR FA9550-20-1-0265. Additionally, the computational part of this work was supported by the Brazilian funding agencies CAPES (finance code 001), CNPq (311353/2019-3) and FAPESP (processes 2012/15147-4 and 2013/07296-2), and the high-performance computer resources provided by the SDumont supercomputer at the National Laboratory for Scientific Computing (LNCC/MCTI, Brazil) and Cloud@UFSCar. We acknowledge the Cambridge Crystallographic Data Centre for the collection of single-crystal data and use of the Mercury software. K.Y. thanks the Japan Society for the Promotion of Science for a JSPS Young Scientist Fellowship and the Overseas Research Program of the Yoshida Foundation for Science and Technology. We also acknowledge the financial support of the University of Michigan College of Engineering and NSF grant no. DMR-0723032, as well as technical support from the Michigan Center for Materials Characterization.

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Author notes

  1. Keiichi Yano

    Present address: Institute of Technology, Shimizu Corporation, Tokyo, Japan

Authors and Affiliations

  1. Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA

    Won Jin Choi, Minjeong Cha, Kai Sun & Nicholas A. Kotov

  2. Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA

    Won Jin Choi, Keiichi Yano, Minjeong Cha, Ji-Young Kim, Yichun Wang, Sang Hyun Lee & Nicholas A. Kotov

  3. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

    Won Jin Choi, Keiichi Yano, Ji-Young Kim, Yichun Wang & Nicholas A. Kotov

  4. Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan

    Keiichi Yano

  5. Brazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, Brazil

    Felippe M. Colombari

  6. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA

    Nicholas A. Kotov

  7. Department of Chemical and Biochemical Engineering, University of Notre Dame, South Bend, IN, USA

    Yichun Wang

  8. Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA

    Sang Hyun Lee

  9. Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA

    John M. Kruger

  10. Department of Chemistry, Federal University of São Carlos, São Carlos, Brazil

    André F. de Moura

  11. Program in Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI, USA

    Nicholas A. Kotov

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Contributions

W.J.C. and N.A.K. designed the project. K.Y. recrystallized the AAs and dipeptides and conducted the PXRD analysis and size distribution analysis. J.-Y.K., W.J.C. and K.S. conducted the SEM and TEM imaging. W.J.C. measured all the THz spectra and developed the algorithm for TA, TCD and TORD. Dynamic time-warping, correlation matrix and violin plots were performed by M.C. W.J.C. and S.H.L. developed the algorithm for the BK theory and S.H.L. conducted the parametric fitting using the nonlinear regression method. F.M.C. and A.F.d.M. conducted the density functional theory simulation and analysed the data. Y.W. performed the MD simulation. J.M.K. removed the cystine stones in clinical purpose and provided them as samples. All the authors discussed the results. W.J.C., A.F.d.M. and N.A.K. wrote the manuscript.

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Correspondence to André F. de Moura or Nicholas A. Kotov.

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Supplementary Information

Supplementary Methods, Discussion, Figs. 1–29 and Tables 1–5.

Supplementary Video 1

Video of single-molecular vibrations.

Supplementary Video 2

Video of chiral phonons.

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Choi, W.J., Yano, K., Cha, M. et al. Chiral phonons in microcrystals and nanofibrils of biomolecules. Nat. Photon. 16, 366–373 (2022). https://doi.org/10.1038/s41566-022-00969-1

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