When Diffraction Stops and Destruction Begins

  • Carl CalemanEmail author
  • Andrew V. Martin


It is now possible to solve protein structures with femtosecond X-ray free-electron laser (XFEL) pulses that were previously inaccessible to continuous synchrotron sources due to radiation damage. The key to this success is that diffraction probes the protein structure on femtosecond timescales, whereas nuclear motion takes tens to hundreds of femtoseconds to have a significant effect on the crystal structure. This is the essential idea behind the diffraction-before-destruction principle that underlies serial femtosecond crystallography (SFX) with XFELs. In practice, the principle works well enough to determine protein structures of comparable resolution to synchrotron protein crystallography, which has led to the many successes of XFEL crystallography to date.


  1. 1.
    Chapman, H. N., Fromme, P., Barty, A., White, T. A., Kirian, R. A., Aquila, A., et al. (2011). Femtosecond X-ray protein nanocrystallography. Nature, 470, 73–77.CrossRefGoogle Scholar
  2. 2.
    Boutet, S., Lomb, L., Williams, G. J., Barends, T. R. M., Aquila, A., Doak, R. B., et al. (2012). High-resolution protein structure determination by serial femtosecond crystallography. Science, 337, 362–364.CrossRefGoogle Scholar
  3. 3.
    Barty, A., Caleman, C., Aquila, A., Timneanu, N., Lomb, L., White, T. A., et al. (2012). Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements. Nature Photonics, 6, 35–40.CrossRefGoogle Scholar
  4. 4.
    Galli, L., Son, S.-K., Klinge, M., Bajt, S., Barty, A., Bean, R., et al. (2015). Electronic damage in S atoms in a native protein crystal induced by an intense X-ray free-electron laser pulse. Structure & Dynamics, 2, 041703.CrossRefGoogle Scholar
  5. 5.
    Nass, K., Foucar, L., Barends, T. R. M., Hartmann, E., Botha, S., Shoeman, R. L., et al. (2015). Indications of radiation damage in ferredoxin microcrystals using high-intensity X-FEL beams. Journal of Synchrotron Radiation, 22, 225–238.CrossRefGoogle Scholar
  6. 6.
    Son, S.-K., Chapman, H. N., & Santra, R. (2011). Multiwavelength anomalous diffraction at high X-ray intensity. Physical Review Letters, 107, 218102.CrossRefGoogle Scholar
  7. 7.
    Martin, A. V., & Quiney, H. M. (2016). Coherence loss by sample dynamics and heterogeneity in X-ray laser diffraction. Journal of Physics B: Atomic, Molecular and Optical Physics, 49, 244001.CrossRefGoogle Scholar
  8. 8.
    Abbey, B., Dilanian, R. A., Darmanin, C., Ryan, R. A., Putkunz, C. T., Martin, A. V., et al. (2016). X-ray laser-induced electron dynamics observed by femtosecond diffraction from nanocrystals of buckminsterfullerene. Science Advances, 2, e1601186.CrossRefGoogle Scholar
  9. 9.
    Ferguson, K. R., Bucher, M., Gorkhover, T., Boutet, S., Fukuzawa, H., Koglin, J. E., et al. (2016). Transient lattice contraction in the solid-to-plasma transition. Science Advances, 2(1), e1500837.CrossRefGoogle Scholar
  10. 10.
    Owen, R. L., Rudiño-Piñera, E., & Garman, E. F. (2006). Experimental determination of the radiation dose limit for cryocooled protein crystals. Proceedings of the National Academy of Sciences of the United States of America, 103, 4912–4917.CrossRefGoogle Scholar
  11. 11.
    Chapman, H. N., Caleman, C., & Timneanu, N. (2014). Diffraction before destruction. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 369, 20130313.CrossRefGoogle Scholar
  12. 12.
    Auger, P., Ehrenfest, R., Maze, R., Daudin, J. & Fréon, R. A. (1939). Extensive Cosmic-Ray showers. Reviews of Modern Physics, 11, 288–291.CrossRefGoogle Scholar
  13. 13.
    X-ray data booklet. revision. Technical report, 1986.Google Scholar
  14. 14.
    Hubbell, J. H., Veigele, W. J., Briggs, E. A., Brown, R. T., Cromer, D. T., & Howerton, R. J. (1975). Atomic form factors, incoherent scattering functions, and photon scattering cross sections. Journal of Physical and Chemical Reference Data, 4, 471–538.CrossRefGoogle Scholar
  15. 15.
    Krause, M. O., & Oliver, J. H. (1979). Natural widths of atomic K and L levels, Kα X-ray lines and several KLL auger lines. Journal of Physical and Chemical Reference Data, 8, 329–338.CrossRefGoogle Scholar
  16. 16.
    Siegbahn, K. (1970). ESCA applied to free molecules. Amsterdam: North-Holland.Google Scholar
  17. 17.
    Persson, P., Lunell, S., Szöke, A., Ziaja, B., & Hajdu, J. (2001). Shake-up and shake-off excitations with associated electron losses in X-ray studies of proteins. Protein Science, 10, 2480–2484.CrossRefGoogle Scholar
  18. 18.
    Caleman, C. (2007). Towards Single Molecule Imaging - Understanding Structural Transitions Using Ultrafast X-Ray Sources and Computer Simulations. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology.Google Scholar
  19. 19.
    Ziaja, B., London, R. A., & Hajdu, J. (2005). Unified model of secondary electron cascades in diamond. Journal of Applied Physics, 97, 064905.CrossRefGoogle Scholar
  20. 20.
    Landau, L. D., & Lifshitz, E. M. (1981). Quantum mechanics: Non-relativistic theory. Amsterdam: Elsevier.Google Scholar
  21. 21.
    Caleman, C., Ortiz, C., Marklund, E., Bultmark, F., Gabrysch, M., Parak, F. G., et al. (2009). Radiation damage in biological material: Electronic properties and electron impact ionization in urea. Europhysics Letters, 85, 18005.CrossRefGoogle Scholar
  22. 22.
    Caleman, C., Huldt, G., Maia, F. R. N. C., Ortiz, C., Parak, F. G., Hajdu, J., et al. (2011). On the feasibility of nanocrystal imaging using intense and ultrashort X-ray pulses. ACS Nano, 5, 139–146.CrossRefGoogle Scholar
  23. 23.
    Young, L., Kanter, E. P., Krässig, B., Li, Y., March, A. M., Pratt, S. T., et al. (2010). Femtosecond electronic response of atoms to ultra-intense X-rays. Nature, 466, 56–61.CrossRefGoogle Scholar
  24. 24.
    Caleman, C., Bergh, M., Scott, H. A., Spence, J. C. H., Chapman, H. N., & Tîmneanu, N. (2011). Simulations of radiation damage in biomolecular nanocrystals induced by femtosecond X-ray pulses. Journal of Modern Optics, 58, 1486–1497.CrossRefGoogle Scholar
  25. 25.
    Caleman, C., Tîmneanu, N., Martin, A. V., Jönsson, H. O., Aquila, A., Barty, A., et al. (2015). Ultrafast self-gating Bragg diffraction of exploding nanocrystals in an X-ray laser. Optics Express, 23, 1213–1231.CrossRefGoogle Scholar
  26. 26.
    Scott, H. A. (2001). Cretin—A radiative transfer capability for laboratory plasmas. Journal of Quantitative Spectroscopy and Radiation Transfer, 71, 689–701.CrossRefGoogle Scholar
  27. 27.
    Book, D. L., & Naval Research Laboratory (U.S.). (1987). NRL plasma formulary.Google Scholar
  28. 28.
    Gericke, D. O., Murillo, M. S., & Schlanges, M. (2002). Dense plasma temperature equilibration in the binary collision approximation. Physical Review E, 65, 036418.CrossRefGoogle Scholar
  29. 29.
    Neutze, R., Wouts, R., van der Spoel, D., Weckert, E., & Hajdu, J. (2000). Potential for biomolecular imaging with femtosecond X-ray pulses. Nature, 406, 752–757.CrossRefGoogle Scholar
  30. 30.
    Hau-Riege, S. P., London, R. A., & Szoke, A. (2004). Dynamics of biological molecules irradiated by short X-ray pulses. Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics, 69, 051906.CrossRefGoogle Scholar
  31. 31.
    Bergh, M., Tîmneanu, N., & van der Spoel, D. (2004). Model for the dynamics of a water cluster in an X-ray free electron laser beam. Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics, 70, 051904.CrossRefGoogle Scholar
  32. 32.
    Jurek, Z., Oszlányi, G., & Faigel, G. (2004). Imaging atom clusters by hard X-ray free-electron lasers. Europhysics Letters, 65, 491–497.CrossRefGoogle Scholar
  33. 33.
    Krejcik, P., Decker, F.-J., Emma, P., Hacker, K., Hendrickson, L., O’Connell, C. L., et al. (2003). Commissioning of the SPPS linac bunch compressor. In: Proceedings of the 2003 particle accelerator conference.Google Scholar
  34. 34.
    Lindenberg, A. M., Larsson, J., Sokolowski-Tinten, K., Gaffney, K. J., Blome, C., Synnergren, O., et al. (2005). Atomic-scale visualization of inertial dynamics. Science, 308(5720), 392–395.CrossRefGoogle Scholar
  35. 35.
    Graziani, F. R., Batista, V. S., Benedict, L. X., Castor, J. I., Chen, H., Chen, S. N., et al. (2012). Large-scale molecular dynamics simulations of dense plasmas: The Cimarron Project. High Energy Density Physics, 8, 105–131.CrossRefGoogle Scholar
  36. 36.
    Hau-Riege, S. P., & Bennion, B. J. (2015). Reproducible radiation-damage processes in proteins irradiated by intense X-ray pulses. Physical Review E, 91, 022705.CrossRefGoogle Scholar
  37. 37.
    Jurek, Z., Son, S.-K., Ziaja, B., & Santra, R. (2016). XMDYN and XATOM: Versatile simulation tools for quantitative modeling of X-ray free-electron laser induced dynamics of matter. Journal of Applied Crystallography, 49, 1048–1056.CrossRefGoogle Scholar
  38. 38.
    Son, S.-K., Young, L., & Santra, R. (2011). Impact of hollow-atom formation on coherent X-ray scattering at high intensity. Physical Review A, 83, 033402.CrossRefGoogle Scholar
  39. 39.
    Jönsson, H. O., Tîmneanu, N., Östlin, C., Scott, H. A., & Caleman, C. (2015). Simulations of radiation damage as a function of the temporal pulse profile in femtosecond X-ray protein crystallography. Journal of Synchrotron Radiation, 22, 256–266.CrossRefGoogle Scholar
  40. 40.
    Waasmaier, D., & Kirfel, A. (1995). New analytical scattering-factor functions for free atoms and ions. Acta Crystallographica. Section A, 51, 416–431.Google Scholar
  41. 41.
    Slater, J. C. (1930). Atomic shielding constants. Physical Review, 36, 57–64.CrossRefGoogle Scholar
  42. 42.
    Quiney, H. M., & Nugent, K. A. (2011). Biomolecular imaging and electronic damage using X-ray free-electron lasers. Nature Physics, 7, 142–146.CrossRefGoogle Scholar
  43. 43.
    Lomb, L., Barends, T. R. M., Kassemeyer, S., Aquila, A., Epp, S. W., Erk, B., et al. (2011). Radiation damage in protein serial femtosecond crystallography using an X-ray free-electron laser. Physical Review B: Condensed Matter and Materials Physics, 84, 214111.CrossRefGoogle Scholar
  44. 44.
    Barends, T. R. M., Foucar, L., Botha, S., Doak, R. B., Shoeman, R. L., Nass, K., et al. (2014). De novo protein crystal structure determination from X-ray free-electron laser data. Nature, 505, 244–247.CrossRefGoogle Scholar
  45. 45.
    Galli, L., Barends, T. R. M., Son, S.-K., White, T. A., Barty, A., Botha, S., et al. (2015). Crystal structure of gadolinium derivative of HEWL solved using Free-Electron laser radiation. IUCrJ, 2, 627–634.CrossRefGoogle Scholar
  46. 46.
    Nakane, T., Song, C., Suzuki, M., Nango, E., Kobayashi, J., Masuda, T., et al. Native sulfur/chlorine SAD phasing for serial femtosecond crystallography. Acta Crystallographica. Section D, Biological Crystallography, 71, 2519–2525 (2015)CrossRefGoogle Scholar
  47. 47.
    Nass, K., Meinhart, A., Barends, T. R. M., Foucar, L., Gorel, A., Aquila, A., et al. (2016). Protein structure determination by single-wavelength anomalous diffraction phasing of X-ray free-electron laser data. IUCrJ, 3, 180–191.CrossRefGoogle Scholar
  48. 48.
    Hunter, M. S., Yoon, C. H., DeMirci, H., Sierra, R. G., Dao, E. H., Ahmadi, R., et al. (2016). Selenium single-wavelength anomalous diffraction de novo phasing using an X-ray-free electron laser. Nature Communications, 7, 13388.CrossRefGoogle Scholar
  49. 49.
    Bortel, G., Faigel, G., & Tegze, M. (2009). Classification and averaging of random orientation single macromolecular diffraction patterns at atomic resolution. Journal of Structural Biology, 166, 226–233.CrossRefGoogle Scholar
  50. 50.
    Aquila, A., Barty, A., Bostedt, C., Boutet, S., Carini, G., dePonte, D., et al. (2015). The linac coherent light source single particle imaging road map. Structural Dynamics, 2(4), 041701.CrossRefGoogle Scholar
  51. 51.
    Ekeberg, T., Svenda, M., Abergel, C., Maia, F. R. N. C., Seltzer, V., Claverie, J.-M., et al. (2015, March). Three-dimensional reconstruction of the giant mimivirus particle with an X-ray free-electron laser. Physical Review Letters, 114, 098102.CrossRefGoogle Scholar
  52. 52.
    Martin, A. V., Corso, J. K., Caleman, C., Timneanu, N., & Quiney, H. M. (2015). Single-molecule imaging with longer X-ray laser pulses. IUCrJ, 2, 661–674.CrossRefGoogle Scholar
  53. 53.
    Hau-Riege, S., London, R., Huldt, G., & Chapman, H. (2005). Pulse requirements for X-ray diffraction imaging of single biological molecules. Physical Review E, 71, 061919.CrossRefGoogle Scholar
  54. 54.
    Hau-Riege, S. P., London, R. A., Chapman, H. N., Szoke, A., & Timneanu, N. (2007). Encapsulation and diffraction-pattern-correction methods to reduce the effect of damage in X-ray diffraction imaging of single biological molecules. Physical Review Letters, 98, 198302.CrossRefGoogle Scholar
  55. 55.
    Hau-Riege, S. P., Boutet, S., Barty, A., Bajt, S., Bogan, M. J., Frank, M., et al. (2010). Sacrificial tamper slows down sample explosion in flash diffraction experiments. Physical Review Letters, 104, 064801.CrossRefGoogle Scholar
  56. 56.
    Lorenz, U., Kabachnik, N. M., Weckert, E.., & Vartanyants, I. A. (2012). Impact of ultrafast electronic damage in single-particle X-ray imaging experiments. Physical Review B, 86, 051911.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Physics and AstronomyUppsala UniversityUppsalaSweden
  2. 2.Center for Free-Electron Laser ScienceDeutsches Elektronen-SynchrotronHamburgGermany
  3. 3.School of ScienceRMIT UniversityMelbourneAustralia
  4. 4.ARC Centre of Excellence for Advanced Molecular ImagingUniversity of MelbourneMelbourneAustralia

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