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Small Is Beautiful: Growth and Detection of Nanocrystals

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X-ray Free Electron Lasers

Abstract

With the advent of X-Ray free electron lasers (FELs), the field of serial femtosecond crystallography (SFX) was borne, allowing a stream of nanocrystals to be measured individually and diffraction data to be collected and merged to form a complete crystallographic data set. This allows submicron to micron crystals to be utilized in an experiment when they were once, at best, only an intermediate result towards larger, usable crystals. SFX and its variants have opened new possibilities in structural biology, including studies with increased temporal resolution, extending to systems with irreversible reactions, and minimizing artifacts related to local radiation damage. Perhaps the most profound aspect of this newly established field is that “molecular movies,” in which the dynamics and kinetics of biomolecules are studied as a function of time, are now an attainable commodity for a broad variety of systems, as discussed in Chaps. 11 and 12. However, one of the historic challenges in crystallography has always been crystallogenesis and this is no exception when preparing samples for serial crystallography methods. In the following chapter, we focus on some of the specific characteristics and considerations inherent in preparing a suitable sample for successful serial crystallographic approaches.

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References

  1. Scopes, R. K. (2013). Protein purification: Principles and practice. Berlin, Germany: Springer.

    Google Scholar 

  2. Doublié, S. (2007). Macromolecular crystallography protocols (Vol. 1). New York: Springer.

    Google Scholar 

  3. Jancarik, J., & Kim, S.-H. (1991). Sparse matrix sampling: A screening method for crystallization of proteins. Journal of Applied Crystallography, 24(4), 409–411.

    Article  CAS  Google Scholar 

  4. Vekilov, P. G., Feeling-Taylor, A., Yau, S.-T., & Petsev, D. (2002). Solvent entropy contribution to the free energy of protein crystallization. Acta Crystallographica Section D: Biological Crystallography, 58(10), 1611–1616.

    Article  Google Scholar 

  5. Garcıa-Ruiz, J. M. (2003). Nucleation of protein crystals. Journal of Structural Biology, 142(1), 22–31.

    Article  Google Scholar 

  6. Perutz, M. F., Rossmann, M. G., Cullis, A. F., Muirhead, H., Will, G., & North, A. (1960). Structure of hæmoglobin: A three-dimensional Fourier synthesis at 5.5-Å. Resolution, obtained by X-ray analysis. Nature, 185(4711), 416–422.

    Article  CAS  Google Scholar 

  7. Giegé, R. (2013). A historical perspective on protein crystallization from 1840 to the present day. The FEBS Journal, 280(24), 6456–6497.

    Article  Google Scholar 

  8. McPherson, A. (2017). Protein crystallization. In Protein Crystallography: Methods and Protocols (pp. 17–50). New York: Springer.

    Chapter  Google Scholar 

  9. Rupp, B. (2009). Biomolecular crystallography: Principles, practice, and application to structural biology. Abingdon, UK: Garland Science.

    Google Scholar 

  10. Cohen, A. E., Soltis, S. M., Gonzalez, A., Aguila, L., Alonso-Mori, R., Barnes, C. O., Baxter, E. L., Brehmer, W., Brewster, A. S., Brunger, A. T., Calero, G., Chang, J. F., Chollet, M., Ehrensberger, P., Eriksson, T. L., Feng, Y., Hattne, J., Hedman, B., Hollenbeck, M., Holton, J. M., Keable, S., Kobilka, B. K., Kovaleva, E. G., Kruse, A. C., Lemke, H. T., Lin, G., Lyubimov, A. Y., Manglik, A., Mathews, I. I., McPhillips, S. E., Nelson, S., Peters, J. W., Sauter, N. K., Smith, C. A., Song, J., Stevenson, H. P., Tsai, Y., Uervirojnangkoorn, M., Vinetsky, V., Wakatsuki, S., Weis, W. I., Zadvornyy, O. A., Zeldin, O. B., Zhu, D., & Hodgson, K. O. (2014). Goniometer-based femtosecond crystallography with X-ray free electron lasers. Proceedings of the National Academy of Sciences of the United States of America, 111(48), 17122–17127.

    Article  CAS  Google Scholar 

  11. Hirata, K., Shinzawa-Itoh, K., Yano, N., Takemura, S., Kato, K., Hatanaka, M., Muramoto, K., Kawahara, T., Tsukihara, T., & Yamashita, E. (2014). Determination of damage-free crystal structure of an X-ray-sensitive protein using an XFEL. Nature Methods, 11(7), 734–736.

    Article  CAS  Google Scholar 

  12. Aquila, A., Hunter, M. S., Doak, R. B., Kirian, R. A., Fromme, P., White, T. A., Andreasson, J., Arnlund, D., Bajt, S., Barends, T. R., Barthelmess, M., Bogan, M. J., Bostedt, C., Bottin, H., Bozek, J. D., Caleman, C., Coppola, N., Davidsson, J., DePonte, D. P., Elser, V., Epp, S. W., Erk, B., Fleckenstein, H., Foucar, L., Frank, M., Fromme, R., Graafsma, H., Grotjohann, I., Gumprecht, L., Hajdu, J., Hampton, C. Y., Hartmann, A., Hartmann, R., Hau-Riege, S., Hauser, G., Huaser, H., Hirsemann, P., Holl, J., Holton, M., Hömke, A., Johansson, L., Kimmel, N., Kassemeyer, S., Krasniqi, F., Kühnel, K.-U., Liang, M., Lomb, L., Malmerberg, E., Marchesini, S., Martin, A. V., Maia, F. R., Messerschmidt, M., Nass, K., Schlichting, I., Schmidt, C., Schmidt, K. E., Schulz, J., Seibert, M. M., Shoeman, R. L., Sierra, R., Soltau, H., Starodub, D., Stellato, F., Stern, S., Strüder, L., Timneanu, N., Ullrich, J., Wang, X., Williams, G. J., Weidenspointner, G., Weierstall, U., Wunderer, C., Barty, A., Spence, J. C. H., & Chapman, H. N. (2012). Time-resolved protein nanocrystallography using an X-ray free-electron laser. Optics Express, 20(3), 2706–2716.

    Google Scholar 

  13. Kupitz, C., Basu, S., Grotjohann, I., Fromme, R., Zatsepin, N. A., Rendek, K. N., Hunter, M. S., Shoeman, R. L., White, T. A., Wang, D., James, D., Yang, J.-H., Cobb, D. E., Reeder, B., Sierra, R. G., Liu, H., Barty, A., Aquila, A. L., Deponte, D., Kirian, R. A., Bari, S., Bergkamp, J. J., Beyerlein, K. R., Bogan, M. J., Caleman, C., Chao, T.-C., Conrad, C. E., Davis, K. M., fleckenstein, H., Galli, L., Hau-Riege, S. P., Kassemeyer, S., Laksmono, H., Liang, M., Lomb, L., Marchesini, S., Martin, A. V., Messerschmidt, M., Milathianaki, D., Nass, K., Ros, A., Roy-Chowdhury, S., Schmidt, K., Seibert, M., Steinbrener, J., Stellato, F., Yan, L., Yoon, C., Moore, T. A., Moore, A. L., Pushkar, Y., Williams, G. J., Boutet, S., Doak, R. B., Weierstall,~U., Frank, M., Chapman, H. N., Spence, J. C. H., & Fromme, P. (2014). Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser. Nature, 513(7517), 261–265.

    Google Scholar 

  14. Pande, K., Hutchinson, C. D. M., Groenhof, G., Aquila, A., Robinson, J. S., Tenboer, J., Basu, S., Boutet, S., Deponte, D., Liang, M., White, T., Zatsepin, N., Yefanov, O., Morozov, D., Oberthuer, D., Gati, C., Subramanian, G., James, D., Zhao, Y., Koralek, J., Brayshaw, J., Kupitz, C., Conrad, C., Roy-Chowdhury, S., Coe, J., Metz, M., Paulraj Lourdu, X., Grant, T., Koglin, J., Ketawala, G., Fromme, R., Srajer, V., Henning, R., Spence, J., Ourmazd, A., Schwander, P., Weierstall, U., Frank, M., Fromme, P., Barty, A., Chapman, H., Moffat, K., Van Thor, J. J., & Schmidt, M. (2016). Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein. Science, 352(6286), 725–729.

    Article  CAS  Google Scholar 

  15. Tenboer, J., Basu, S., Zatsepin, N., Pande, K., Milathianaki, D., Frank, M., Hunter, M., Boutet, S., Williams, G. J., Koglin, J. E., Oberthuer, D., Heymann, M., Kupitz, C., Conrad, C., Coe, J., Roy-Chowdhury, S., Weierstall, U., James, D., Wang, D., Grant, T., Barty, A., Yefanov, O., Scales, J., Gati, C., Seuring, C., Srajer, V., Henning, R., Schwander, P., Fromme, R., Ourmazd, A., Moffat, K., Van Thor, J. J., Spence, J. C. H., Fromme, P., Chapman, H. N., & Schmidt, M. (2014). Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein. Science, 346(6214), 1242–1246.

    Article  CAS  Google Scholar 

  16. Kupitz, C., Grotjohann, I., Conrad, C. E., Roy-Chowdhury, S., Fromme, R., & Fromme, P. (2014). Microcrystallization techniques for serial femtosecond crystallography using photosystem II from thermosynechococcus elongatus as a model system. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1647), 20130316.

    Article  Google Scholar 

  17. Salemme, F. (1972). A free interface diffusion technique for the crystallization of proteins for X-ray crystallography. Archives of Biochemistry and Biophysics, 151(2), 533–539.

    Article  CAS  Google Scholar 

  18. Abdallah, B. G., Roy-Chowdhury, S., Fromme, R., Fromme, P., & Ros, A. (2016). Protein crystallization in an actuated microfluidic nanowell device. Crystal Growth & Design, 16, 2074–2082.

    Article  CAS  Google Scholar 

  19. Kupitz, C., Olmos, J. L., Jr., Holl, M., Tremblay, L., Pande, K., Pandey, S., Oberthür, D., Hunter, M., Liang, M., Aquila, A., Tenboer, J., Calvey, G., Katz, A., Chen, Y., Wiedorn, M. O., Knoska, J., Meents, A., Mariani, V., Norwood, T., Poudyal, I., Grant, T., Miller, M. D., Xu, W., Tolstikova, A., Morgan, A., Metz, M., Martin-Garcia, J. M., Zook, J. D., Roy-Chowdhury, S., Coe, J., Nagaratnam, N., Meza, D., Fromme, R., Basu, S., Frank, M., White, T., Barty, A., Bajt, S., Yefanov, O., Chapman, H. N., Zatsepin, N., Nelson, G., Weierstall, U., Spence, J., Schwander, P., Pollack, L., Fromme, P., Ourmazd, A., Phillips, G. N., & Schmidt, M. (2017). Structural enzymology using X-ray free electron lasers. Structural Dynamics, 4(4), 044003.

    Google Scholar 

  20. Redecke, L., Nass, K., DePonte, D. P., White, T. A., Rehders, D., Barty, A., Stellato, F., Liang, M., Barends, T. R., Boutet, S., Williams, G. J., Messerschmidt, M., Seibert, M. M., Aquila, A., Arnlund, D., Bajt, S., Barth, T., Bogan, M. J., Caleman, C., Chao, T. C., Doak, R. B., Fleckenstein, H., Frank, M., Fromme, R., Galli, L., Grotjohann, I., Hunter, M. S., Johansson, L. C., Kassemeyer, S., Katona, G., Kirian, R. A., Koopmann, R., Kupitz, C., Lomb, L., Martin, A. V., Mogk, S., Neutze, R., Shoeman, R. L., Steinbrener, J., Timneanu, N., Wang, D., Weierstall, U., Zatsepin, N. A., Spence, J. C., Fromme, P., Schlichting, I., Duszenko, M., Betzel, C., & Chapman, H. N. (2013). Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser. Science, 339(6116), 227–230.

    Article  CAS  Google Scholar 

  21. Sawaya, M. R., Cascio, D., Gingery, M., Rodriguez, J., Goldschmidt, L., Colletier, J. P., Messerschmidt, M. M., Boutet, S., Koglin, J. E., Williams, G. J., Brewster, A. S., Nass, K., Hattne, J., Botha, S., Doak, R. B., Shoeman, R. L., DePonte, D. P., Park, H. W., Federici, B. A., Sauter, N. K., Schlichting, I., & Eisenberg, D. S. (2014). Protein crystal structure obtained at 2.9 a resolution from injecting bacterial cells into an X-ray free-electron laser beam. Proceedings of the National Academy of Sciences of the United States of America, 111(35), 12769–12774.

    Article  CAS  Google Scholar 

  22. Ostermeier, C., & Michel, H. (1997). Crystallization of membrane proteins. Current Opinion in Structural Biology, 7(5), 697–701.

    Article  CAS  Google Scholar 

  23. Fromme, R., Ishchenko, A., Metz, M., Chowdhury, S. R., Basu, S., Boutet, S., Fromme, P., White, T. A., Barty, A., Spence, J. C., Weierstall, U., Liu, W., & Cherezov, V. (2015). Serial femtosecond crystallography of soluble proteins in lipidic cubic phase. IUCrJ, 2(5), 545–551.

    Article  CAS  Google Scholar 

  24. Martin-Garcia, J. M., Conrad, C. E., Nelson, G., Stander, N., Zatsepin, N. A., Zook, J., Zhu, L., Geiger, J., Chun, E., Kissick, D., Hilgart, M. C., Ogata, C., Ishchenko, A., Nagaratnam, N., Roy-Chowdhury, S., Coe, J., Subramanian, G., Schaffer, A., James, D., Ketawala, G., Venugopalan, N., Xu, S., Corcoran, S., Ferguson, D., Weierstall, U., Spence, J. C. H., Cherezov, V., Fromme, P., Fischetti, R. F., & Liu, W. (2017). Serial millisecond crystallography of membrane and soluble protein microcrystals using synchrotron radiation. IUCrJ, 4(4), 439–454.

    Google Scholar 

  25. Weierstall, U., James, D., Wang, C., White, T. A., Wang, D., Liu, W., Spence, J. C., Doak, R. B., Nelson, G., & Fromme, P. (2014). Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nature Communications, 5, 3309.

    Article  Google Scholar 

  26. Ibrahim, M., Chatterjee, R., Hellmich, J., Tran, R., Bommer, M., Yachandra, V. K., Yano, J., Kern, J., & Zouni, A. (2015). Improvements in serial femtosecond crystallography of photosystem II by optimizing crystal uniformity using microseeding procedures. Structural Dynamics, 2(4), 041705.

    Article  Google Scholar 

  27. Kirian, R. A., Wang, X., Weierstall, U., Schmidt, K. E., Spence, J. C., Hunter, M., Fromme, P., White, T., Chapman, H. N., & Holton, J. (2010). Femtosecond protein nanocrystallography—Data analysis methods. Optics Express, 18(6), 5713–5723.

    Article  Google Scholar 

  28. Uervirojnangkoorn, M., Zeldin, O. B., Lyubimov, A. Y., Hattne, J., Brewster, A. S., Sauter, N. K., Brunger, A. T., & Weis, W. I. (2015). Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals. eLife, 4, e05421.

    Article  Google Scholar 

  29. Ginn, H. M., Brewster, A. S., Hattne, J., Evans, G., Wagner, A., Grimes, J. M., Sauter, N. K., Sutton, G., & Stuart, D. (2015). A revised partiality model and post-refinement algorithm for X-ray free-electron laser data. Acta Crystallographica Section D: Biological Crystallography, 71(6), 1400–1410.

    Article  CAS  Google Scholar 

  30. Ginn, H. M., Messerschmidt, M., Ji, X., Zhang, H., Axford, D., Gildea, R. J., Winter, G., Brewster, A. S., Hattne, J., Wagner, A., Grimes, J. M., Evans, G., Sauter, N. K., Sutton, G., & Stuart, D. I. (2015). Structure of CPV17 polyhedrin determined by the improved analysis of serial femtosecond crystallographic data. Nature Communications, 6.

    Google Scholar 

  31. Spence, J. C. H., Weierstall, U., & Chapman, H. N. (2012). X-ray lasers for structural and dynamic biology. Reports on Progress in Physics, 75(10), 102601.

    Article  CAS  Google Scholar 

  32. Brehms, W., & Diederichs, K. (2014). Breaking the indexing ambiguity in serial crystallography. Acta Crystallographica Section D, D70, 101–109.

    Article  Google Scholar 

  33. Abdallah, B. G., Zatsepin, N. A., Roy-Chowdhury, S., Coe, J., Conrad, C. E., Dörner, K., Sierra, R. G., Stevenson, H. P., Grant, T. D., Nelson, G., James, D. R., Calero, G., Wachter, R. M., Spence, J. C. H., Weierstall, U., Fromme, P., & Ros, A. (2015). Microfluidic sorting of protein nanocrystals by size for XFEL diffraction. Structural Dynamics, 2, 041719.

    Article  Google Scholar 

  34. Abdallah, B. G., Chao, T. C., Kupitz, C., Fromme, P., & Ros, A. (2013). Dielectrophoretic sorting of membrane protein nanocrystals. American Chemical Society Nano, 7(10), 9129–9137.

    CAS  PubMed  Google Scholar 

  35. Haupert, L. M., & Simpson, G. J. (2011). Screening of protein crystallization trials by second order nonlinear optical imaging of chiral crystals (SONICC). Methods, 55(4), 379–386.

    Article  CAS  Google Scholar 

  36. Kissick, D. J., Wanapun, D., & Simpson, G. J. (2011). Second-order nonlinear optical imaging of chiral crystals. Annual Review of Analytical Chemistry, 4, 419.

    Article  CAS  Google Scholar 

  37. Madden, J. T., DeWalt, E. L., & Simpson, G. J. (2011). Two-photon excited UV fluorescence for protein crystal detection. Acta Crystallographica Section D: Biological Crystallography, 67(10), 839–846.

    Article  CAS  Google Scholar 

  38. Pecora, R. (2000). Dynamic light scattering measurement of nanometer particles in liquids. Journal of Nanoparticle Research, 2(2), 123–131.

    Article  CAS  Google Scholar 

  39. Schubert, R., Meyer, A., Dierks, K., Kapis, S., Reimer, R., Einspahr, H., Perbandt, M., & Betzel, C. (2015). Reliably distinguishing protein nanocrystals from amorphous precipitate by means of depolarized dynamic light scattering. Journal of Applied Crystallography, 48(5), 1476–1484.

    Article  CAS  Google Scholar 

  40. Schmitz, K. S. (1990). An introduction to dynamic light scattering of macromolecules. Kansas City, MO: University of Missouri.

    Google Scholar 

  41. Rasband, W. (1997). ImageJ. Bethesda, MD: US National Institutes of Health.

    Google Scholar 

  42. Bai, K., Barnett, G. V., Kar, S. R., & Das, T. K. (2017). Interference from proteins and surfactants on particle size distributions measured by nanoparticle tracking analysis (NTA). Pharmaceutical Research, 34(4), 800–808.

    Article  CAS  Google Scholar 

  43. Regtmeier, J., Eichhorn, R., Duong, T. T., Anselmetti, D., & Ros, A. (2007). Dielectrophoretic manipulation of DNA: Separation and polarizability. Analytical Chemistry, 79, 3925–3932.

    Article  CAS  Google Scholar 

  44. Stevenson, H. P., Lin, G. W., Barnes, C. O., Sutkeviciute, I., Krzysiak, T., Weiss, S. C., Reynolds, S., Wu, Y., Nagarajan, V., Makhov, A. M., Lawrence, R., Lamm, E., Clark, L., Gardella, T. J., Hogue, B. G., Ogata, C. M., Ahn, J., Gronenborn, A. M., Conway, J. F., Vilardaga, J. P., Cohen, A. E., & Calero, G. (2016). Transmission electron microscopy for the evaluation and optimization of crystal growth. Acta Crystallographica Section D-Structural Biology, 72, 603–615.

    Article  CAS  Google Scholar 

  45. Stevenson, H. P., Makhov, A. M., Calero, M., Edwards, A. L., Zeldin, O. B., Mathews, I. I., Lin, G., Barnes, C. O., Santamaria, H., Ross, T. M., Soltis, S. M., Khosla, C., Nagarajan, V., Conway, J. F., Cohen, A. E., & Calero, G. (2014). Use of transmission electron microscopy to identify nanocrystals of challenging protein targets. Proceedings of the National Academy of Sciences of the United States of America, 111(23), 8470–8475.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, CA, USA

    Jesse Coe

  2. School of Molecular Sciences, Arizona State University, Tempe, AZ, USA

    Alexandra Ros

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  1. SLAC National Accelerator Laboratory, Menlo Park, CA, USA

    Sébastien Boutet

  2. School of Molecular Sciences, Arizona State University, Tempe, AZ, USA

    Petra Fromme

  3. SLAC National Accelerator Laboratory, Menlo Park, CA, USA

    Mark S. Hunter

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Coe, J., Ros, A. (2018). Small Is Beautiful: Growth and Detection of Nanocrystals. In: Boutet, S., Fromme, P., Hunter, M. (eds) X-ray Free Electron Lasers. Springer, Cham. https://doi.org/10.1007/978-3-030-00551-1_3

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