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Visualization of Intracellular Elements Using Scanning X-Ray Fluorescence Microscopy

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Abstract

Recent technological developments have enabled the imaging of chemical elements in cells, although quantitative analyses, such as by inductively coupled plasma mass spectrometry, were developed previously. Applications allowing high-resolution imaging at the single-cell level are anticipated in cell biology and medicine, where the roles of elements, especially in relation to intracellular molecules such as proteins, nucleic acids, lipids, and sugars, are essential for understanding cellular functions. The expression of proteins and genes varies depending on cellular function, and multiple elements are likely to be associated with biological molecules in the functioning of cell proliferation, differentiation, aging, and stress responses. In this review, we describe a scanning X-ray fluorescence microscopy system, which can reliably determine the cellular distribution of multiple elements by a sub-100-nm focusing approach, together with its applications. Visualizing intracellular elements and understanding their dynamics at the single-cell level may provide great insight into their behaviors.

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References

  1. Crone B, Aschner M, Schwerdtle T et al (2015) Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS. Metallomics 7(7):1189–1195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Godinho RM, Cabrita MT, Alves LC et al (2014) Imaging of intracellular metal partitioning in marine diatoms exposed to metal pollution: consequences to cellular toxicity and metal fate in the environment. Metallomics 6(9):1626–1631

    Article  CAS  PubMed  Google Scholar 

  3. Thompson CM, Seiter J, Chappell MA et al (2015) Synchrotron-based imaging of chromium and gamma-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water. Toxicol Sci 143(1):16–25

    Article  CAS  PubMed  Google Scholar 

  4. Shimura M, Saito A, Matsuyama S et al (2005) Element array by scanning X-ray fluorescence microscopy after cis-diamminedichloro-platinum(II) treatment. Cancer Res 65(12):4998–5002

    Article  CAS  PubMed  Google Scholar 

  5. Szyrwiel L, Shimura M, Shirataki J et al (2015) A novel branched TAT(47–57) peptide for selective Ni(2+) introduction into the human fibrosarcoma cell nucleus. Metallomics 7(7):1155–1162

    Article  CAS  PubMed  Google Scholar 

  6. Blackiston DJ, McLaughlin KA, Levin M (2009) Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle. Cell Cycle 8(21):3527–3536

    Article  CAS  PubMed  Google Scholar 

  7. Zhang J, Wei J, He Q et al (2015) SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca(2+) signaling in nasopharyngeal carcinoma cells. Onco Targets Ther 8:3123–3133

    Article  PubMed  PubMed Central  Google Scholar 

  8. Jourdan E, Marie Jeanne R, Regine S et al (2004) Zinc-metallothionein genoprotective effect is independent of the glutathione depletion in HaCaT keratinocytes after solar light irradiation. J Cell Biochem 92(3):631–640

    Article  CAS  PubMed  Google Scholar 

  9. Klug A (2010) The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation. Q Rev Biophys 43(1):1–21

    Article  CAS  PubMed  Google Scholar 

  10. Mantler M, Schreiner M (2000) X-ray fluorescence spectrometry in art and archaeology. X-Ray Spectrom 29(1):3–17

    Article  CAS  Google Scholar 

  11. Tanaka T SPECTRA synchrotron radiation calculation code. SPring-8 Center, Hyogo, pp 679–5148. http://radiant.harima.riken.go.jp/spectra/index.html

  12. Matsuyama S, Mimura H, Yumoto H et al (2006) Development of scanning x-ray fluorescence microscope with spatial resolution of 30nm using Kirkpatrick-Baez mirror optics. Rev Sci Instrum 77(10):103102

    Article  Google Scholar 

  13. Yamauchi K, Mimura H, Inagaki K et al (2002) Figuring with subnanometer-level accuracy by numerically controlled elastic emission machining. Rev Sci Instrum 73(11):4028–4033

    Article  CAS  Google Scholar 

  14. Matsuyama S, Mimura H, Yumoto H et al (2006) Development of mirror manipulator for hard-x-ray nanofocusing at sub-50-nm level. Rev Sci Instrum 77(9):093107

    Article  Google Scholar 

  15. Matsuyama S, Shimura M, Mirnura H et al (2009) Trace element mapping of a single cell using a hard x-ray nanobeam focused by a Kirkpatrick-Baez mirror system. X-Ray Spectrom 38(2):89–94

    Article  CAS  Google Scholar 

  16. Matsuyama S, Mimura H, Katagishi K et al (2008) Trace element mapping using a high-resolution scanning X-ray fluorescence microscope equipped with a Kirkpatrick-Baez mirror system. Surf Interface Anal 40(6–7):1042–1045

    Article  CAS  Google Scholar 

  17. Walther P, Studer D, McDonald K (2007) High pressure freezing tutorial. Microsc Microanal 13(S02):440–441

    Google Scholar 

  18. Matsuyama S, Shimura M, Fujii M et al (2010) Elemental mapping of frozen-hydrated cells with cryo-scanning X-ray fluorescence microscopy. X-Ray Spectrom 39(4):260–266

    Article  CAS  Google Scholar 

  19. Griffiths G, SLOT JW, Webster P (2015) Kiyoteru Tokuyasu: a pioneer of cryo-ultramicrotomy. J Microsc 260(3):235–237

    Article  PubMed  Google Scholar 

  20. Egedahl R, Coppock E, Homik R (1991) Mortality experience at a hydrometallurgical nickel refinery in Fort Saskatchewan, Alberta between 1954 and 1984. Occup Med 41(1):29–33

    Article  CAS  Google Scholar 

  21. Gentry SN, Jackson TL (2013) A mathematical model of cancer stem cell driven tumor initiation: implications of niche size and loss of homeostatic regulatory mechanisms. PLoS One 8:e71128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cameron KS, Buchner V, Tchounwou PB (2011) Exploring the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity: a literature review. Rev Environ Health 26(2):81–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Costa M, Klein CB (1999) Nickel carcinogenesis, mutation, epigenetics, or selection. Environ Health Perspect 107(9):A438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Salnikow K, Kasprzak KS (2007) In: Sigel A, Sigel H, Sigel RK (eds) Nickel and its surprising impact in nature: metal ions in life sciences, vol 2. Wiley, Chichester, pp 581–618

    Chapter  Google Scholar 

  25. Das KK, Büchner V (2007) Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health 22(2):157–173

    Article  CAS  PubMed  Google Scholar 

  26. Milletti F (2012) Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today 17(15):850–860

    Article  CAS  PubMed  Google Scholar 

  27. Welser K, Campbell F, Kudsiova L et al (2012) Gene delivery using ternary lipopolyplexes incorporating branched cationic peptides: the role of peptide sequence and branching. Mol Pharm 10(1):127–141

    Article  PubMed  Google Scholar 

  28. Liu Y, Kim YJ, Ji M et al (2014) Enhancing gene delivery of adeno-associated viruses by cell-permeable peptides. Mol Ther Methods Clin Dev 1:1–12

    Article  Google Scholar 

  29. Sakhrani NM, Padh H (2013) Organelle targeting: third level of drug targeting. Drug Des Dev Ther 7:585

    CAS  Google Scholar 

  30. Polyakov V, Sharma V, Dahlheimer JL et al (2000) Novel Tat-peptide chelates for direct transduction of technetium-99m and rhenium into human cells for imaging and radiotherapy. Bioconjug Chem 11(6):762–771

    Article  CAS  PubMed  Google Scholar 

  31. Bullok KE, Dyszlewski M, Prior JL et al (2002) Characterization of novel Histidine-tagged tat-peptide complexes dual-labeled with 99mTc-tricarbonyl and fluorescein for scintigraphy and fluorescence microscopy. Bioconjug Chem 13(6):1226–1237

    Article  CAS  PubMed  Google Scholar 

  32. Zhao M, Weissleder R (2004) Intracellular cargo delivery using tat peptide and derivatives. Med Res Rev 24(1):1–12

    Article  PubMed  Google Scholar 

  33. Eggimann GA, Blattes E, Buschor S et al (2014) Designed cell penetrating peptide dendrimers efficiently internalize cargo into cells. Chem Commun 50(55):7254–7257

    Article  CAS  Google Scholar 

  34. Eggimann GA, Buschor S, Darbre T et al (2013) Convergent synthesis and cellular uptake of multivalent cell penetrating peptides derived from Tat, Antp, pVEC, TP10 and SAP. Org Biomol Chem 11(39):6717–6733

    Article  CAS  PubMed  Google Scholar 

  35. Szyrwiel Ł, Szczukowski Ł, Pap JS et al (2014) The Cu2+ binding properties of branched peptides based on l-2, 3-diaminopropionic acid. Inorg Chem 53(15):7951–7959

    Article  CAS  PubMed  Google Scholar 

  36. Szyrwiel Ł, Pap JS, Szczukowski Ł et al (2015) Branched peptide with three histidines for the promotion of Cu II binding in a wide pH range–complementary potentiometric, spectroscopic and electrochemical studies. RSC Adv 5(70):56922–56931

    Article  CAS  Google Scholar 

  37. AbrreyáMonreal I (2015) Branched dimerization of Tat peptide improves permeability to HeLa and hippocampal neuronal cells. Chem Commun 51(25):5463–5466

    Article  Google Scholar 

  38. Wynn JE, Santos WL (2015) HIV-1 drug discovery: targeting folded RNA structures with branched peptides. Org Biomol Chem 13(21):5848–5858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Eriksson M, van der Veen JF, Quitmann C (2014) Diffraction-limited storage rings-a window to the science of tomorrow. J Synchrotron Radiat 21(5):837–842

    Article  CAS  PubMed  Google Scholar 

  40. Yabashi M, Tono K, Mimura H et al (2014) Optics for coherent X-ray applications. J Synchrotron Radiat 21(5):976–985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Huang X, Yan H, Nazaretski E et al (2013) 11 nm hard X-ray focus from a large-aperture multilayer Laue lens. Sci Rep 3:3562

    PubMed  PubMed Central  Google Scholar 

  42. Mimura H, Handa S, Kimura T et al (2010) Breaking the 10 nm barrier in hard-X-ray focusing. Nat Phys 6(2):122–125

    Article  CAS  Google Scholar 

  43. Yamauchi K, Mimura H, Kimura T et al (2011) Single-nanometer focusing of hard x-rays by Kirkpatrick–Baez mirrors. J Phys Condens Matter 23(39):394206

    Article  PubMed  Google Scholar 

  44. Goto T, Nakamori H, Kimura T et al (2015) Hard X-ray nanofocusing using adaptive focusing optics based on piezoelectric deformable mirrors. Rev Sci Instrum 86(4):043102

    Article  PubMed  Google Scholar 

  45. Hirokatsu Y, Takahisa K, Satoshi M, Kazuto Y, Haruhiko O (2016) Stitching interferometry for ellipsoidal x-ray mirrors. Rev Sci Instrum 87:051905

    Article  Google Scholar 

  46. Matsuyama S, Kidani N, Mimura H et al (2012) Hard-X-ray imaging optics based on four aspherical mirrors with 50 nm resolution. Opt Express 20(9):10310–10319

    Article  PubMed  Google Scholar 

  47. Rubin M, Medeiros-Ribeiro G, O’shea J et al (1996) Imaging and spectroscopy of single InAs self-assembled quantum dots using ballistic electron emission microscopy. Phys Rev Lett 77(26):5268

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

We would like to thank Tetsuya Ishikawa at RIKEN for providing advice and encouragement during this study. We also acknowledge the help of Akihiro Matsunaga at the NCGM for the measurements and analyses of images, Shotaro Hagiwara at the NCGM hospital for clinical studies, and Yoshinori Nishino at Hokkaido University and Yoshiki Kohmura at RIKEN for assistance with the beamline adjustment. This study was supported by CREST from the Japan Science and Technology Agency (MS, SM, LS); MS was supported by a Grant-in-Aid for Research on Advanced Medical Technology, Ministry of Health, and Labor and Welfare of Japan; LS was supported by a Marie Curie Intra-European Fellowship from the European Union (PIEF-GA-2012-329969).

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Correspondence to Mari Shimura .

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Shimura, M., Szyrwiel, L., Matsuyama, S., Yamauchi, K. (2017). Visualization of Intracellular Elements Using Scanning X-Ray Fluorescence Microscopy. In: Ogra, Y., Hirata, T. (eds) Metallomics. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56463-8_3

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