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Enhancing Metabolite Coverage for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Through Multiple On-Tissue Chemical Derivatizations

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Mass Spectrometry Imaging of Small Molecules

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2437))

Abstract

The ability to study and visualize metabolites on a cellular and sub-cellular level is important for gaining insights into biological pathways and metabolism of multicellular organisms. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is a powerful analytical tool for metabolomics experiments due to its high sensitivity and small sampling size. The spatial resolution in MALDI-MSI is mainly limited by the number of molecules available in a small sampling size. When the sampling size is low enough to achieve cellular or subcellular spatial resolution, signal intensity is sacrificed making poorly ionized metabolites difficult to detect. To overcome this limitation, on-tissue chemical derivatization reactions have been used to enhance the desorption/ionization efficiency of selected classes of compounds by adding a functional group with a permanent positive charge or one that can be easily ionized. By utilizing several chemical derivatizations in parallel, metabolite coverage can be drastically improved. This chapter outlines methodology for sample preparation and data analysis for on-tissue chemical derivatization using various derivatization reagents.

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References

  1. Nilsson A, Fehniger TE, Gustavsson L, Andersson M, Kenne K, Marko-Varga G, Andrén PE (2010) Fine mapping the spatial distribution and concentration of unlabeled drugs within tissue micro-compartments using imaging mass spectrometry. PLoS One 5(7):e11411

    Article  Google Scholar 

  2. Castellino S, Groseclose MR, Wagner D (2011) MALDI imaging mass spectrometry: bridging biology and chemistry in drug development. Bioanalysis 3(21):2427–2441. https://doi.org/10.4155/bio.11.232

    Article  CAS  PubMed  Google Scholar 

  3. Shimma S, Sugiura Y, Hayasaka T, Hoshikawa Y, Noda T, Setou M (2007) MALDI-based imaging mass spectrometry revealed abnormal distribution of phospholipids in colon cancer liver metastasis. J Chromatogr B 855(1):98–103. https://doi.org/10.1016/j.jchromb.2007.02.037

    Article  CAS  Google Scholar 

  4. Gónzalez de San Román E, Manuel I, Giralt MT, Ferrer I, Rodríguez-Puertas R (2017) Imaging mass spectrometry (IMS) of cortical lipids from preclinical to severe stages of Alzheimer’s disease. Biochim Biophys Acta 1859(9, Part B):1604–1614. https://doi.org/10.1016/j.bbamem.2017.05.009

    Article  CAS  Google Scholar 

  5. Roux A, Muller L, Jackson SN, Post J, Baldwin K, Hoffer B, Balaban CD, Barbacci D, Schultz JA, Gouty S, Cox BM, Woods AS (2016) Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury. J Neurosci Methods 272:19–32. https://doi.org/10.1016/j.jneumeth.2016.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Black AP, Angel PM, Drake RR, Mehta AS (2019) Antibody panel based N-glycan imaging for N-glycoprotein biomarker discovery. Curr Protoc Protein Sci 98(1):e99. https://doi.org/10.1002/cpps.99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lee YJ, Perdian DC, Song Z, Yeung ES, Nikolau BJ (2012) Use of mass spectrometry for imaging metabolites in plants. Plant J 70(1):81–95. https://doi.org/10.1111/j.1365-313X.2012.04899.x

    Article  CAS  PubMed  Google Scholar 

  8. Francese S, Bradshaw R, Ferguson LS, Wolstenholme R, Clench MR, Bleay S (2013) Beyond the ridge pattern: multi-informative analysis of latent fingermarks by MALDI mass spectrometry. Analyst 138(15):4215–4228. https://doi.org/10.1039/c3an36896c

    Article  CAS  PubMed  Google Scholar 

  9. Korte AR, Yandeau-Nelson MD, Nikolau BJ, Lee YJ (2015) Subcellular-level resolution MALDI-MS imaging of maize leaf metabolites by MALDI-linear ion trap-Orbitrap mass spectrometer. Anal Bioanal Chem 407(8):2301–2309. https://doi.org/10.1007/s00216-015-8460-5

    Article  CAS  PubMed  Google Scholar 

  10. Zavalin A, Yang J, Caprioli R (2013) Laser beam filtration for high spatial resolution MALDI imaging mass spectrometry. J Am Soc Mass Spectrom 24(7):1153–1156. https://doi.org/10.1007/s13361-013-0638-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zavalin A, Todd EM, Rawhouser PD, Yang J, Norris JL, Caprioli RM (2012) Direct imaging of single cells and tissue at sub-cellular spatial resolution using transmission geometry MALDI MS. J Mass Spectrom 47(11):i. https://doi.org/10.1002/jms.3132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Niehaus M, Soltwisch J, Belov ME, Dreisewerd K (2019) Transmission-mode MALDI-2 mass spectrometry imaging of cells and tissues at subcellular resolution. Nat Methods 16(9):925–931. https://doi.org/10.1038/s41592-019-0536-2

    Article  CAS  PubMed  Google Scholar 

  13. Feenstra AD, Dueñas ME, Lee YJ (2017) Five micron high resolution MALDI mass spectrometry imaging with simple, interchangeable, multi-resolution optical system. J Am Soc Mass Spectrom 28(3):434–442. https://doi.org/10.1007/s13361-016-1577-8

    Article  CAS  PubMed  Google Scholar 

  14. Dueñas ME, Larson EA, Lee YJ (2019) Toward mass spectrometry imaging in the metabolomics scale: increasing metabolic coverage through multiple on-tissue chemical modifications. Front Plant Sci 10:860

    Article  Google Scholar 

  15. Dueñas ME, Klein AT, Alexander LE, Yandeau-Nelson MD, Nikolau BJ, Lee YJ (2017) High spatial resolution mass spectrometry imaging reveals the genetically programmed, developmental modification of the distribution of thylakoid membrane lipids among individual cells of maize leaf. Plant J 89(4):825–838. https://doi.org/10.1111/tpj.13422

    Article  CAS  PubMed  Google Scholar 

  16. Feenstra AD, Alexander LE, Song Z, Korte AR, Yandeau-Nelson MD, Nikolau BJ, Lee YJ (2017) Spatial mapping and profiling of metabolite distributions during germination. Plant Physiol 174(4):2532. https://doi.org/10.1104/pp.17.00652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dueñas ME, Carlucci L, Lee YJ (2016) Matrix recrystallization for MALDI-MS imaging of maize lipids at high-spatial resolution. J Am Soc Mass Spectrom 27(9):1575–1578. https://doi.org/10.1007/s13361-016-1422-0

    Article  CAS  PubMed  Google Scholar 

  18. Dueñas ME, Feenstra AD, Korte AR, Hinners P, Lee YJ (2018) Cellular and subcellular level localization of maize lipids and metabolites using high-spatial resolution MALDI mass spectrometry imaging. In: Lagrimini LM (ed) Maize: methods and protocols. Springer New York, New York, NY, pp 217–231. https://doi.org/10.1007/978-1-4939-7315-6_13

    Chapter  Google Scholar 

  19. Hansen RL, Guo H, Yin Y, Lee YJ (2019) FERONIA mutation induces high levels of chloroplast-localized Arabidopsides which are involved in root growth. Plant J 97(2):341–351. https://doi.org/10.1111/tpj.14123

    Article  CAS  PubMed  Google Scholar 

  20. Manier ML, Spraggins JM, Reyzer ML, Norris JL, Caprioli RMCJMSR (2014) A derivatization and validation strategy for determining the spatial localization of endogenous amine metabolites in tissues using MALDI imaging mass spectrometry. J Mass Spectrom 49(8):665–673. https://doi.org/10.1002/jms.3411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Esteve C, Tolner EA, Shyti R, van den Maagdenberg AMJM, McDonnell LA (2016) Mass spectrometry imaging of amino neurotransmitters: a comparison of derivatization methods and application in mouse brain tissue. Metabolomics 12(2):30. https://doi.org/10.1007/s11306-015-0926-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shimma S, Kumada H-O, Taniguchi H, Konno A, Yao I, Furuta K, Matsuda T, Ito S (2016) Microscopic visualization of testosterone in mouse testis by use of imaging mass spectrometry. Anal Bioanal Chem 408(27):7607–7615. https://doi.org/10.1007/s00216-016-9594-9

    Article  CAS  PubMed  Google Scholar 

  23. Cobice DF, Livingstone DEW, Mackay CL, Goodwin RJA, Smith LB, Walker BR, Andrew R (2016) Spatial localization and quantitation of androgens in mouse testis by mass spectrometry imaging. Anal Chem 88(21):10362–10367. https://doi.org/10.1021/acs.analchem.6b02242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Barré FPY, Flinders B, Garcia JP, Jansen I, Huizing LRS, Porta T, Creemers LB, Heeren RMA, Cillero-Pastor B (2016) Derivatization strategies for the detection of triamcinolone acetonide in cartilage by using matrix-assisted laser desorption/ionization mass spectrometry imaging. Anal Chem 88(24):12051–12059. https://doi.org/10.1021/acs.analchem.6b02491

    Article  CAS  PubMed  Google Scholar 

  25. Wu Q, Comi TJ, Li B, Rubakhin SS, Sweedler JV (2016) On-tissue derivatization via electrospray deposition for matrix-assisted laser desorption/ionization mass spectrometry imaging of endogenous fatty acids in rat brain tissues. Anal Chem 88(11):5988–5995. https://doi.org/10.1021/acs.analchem.6b01021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hansen RL, Dueñas ME, Lee YJ (2019) Sputter-coated metal screening for small molecule analysis and high-spatial resolution imaging in laser desorption ionization mass spectrometry. J Am Soc Mass Spectrom 30(2):299–308. https://doi.org/10.1007/s13361-018-2081-0

    Article  CAS  PubMed  Google Scholar 

  27. Korte AR, Yagnik GB, Feenstra AD, Lee YJ (2015) Multiplex MALDI-MS imaging of plant metabolites using a hybrid MS system. In: Mass spectrometry imaging of small molecules. Springer New York, New York, NY, pp 49–62. https://doi.org/10.1007/978-1-4939-1357-2_6

    Chapter  Google Scholar 

  28. Robichaud G, Garrard KP, Barry JA, Muddiman DC (2013) MSiReader: an open-source Interface to view and analyze high resolving power MS imaging files on Matlab platform. J Am Soc Mass Spectrom 24(5):718–721. https://doi.org/10.1007/s13361-013-0607-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dannhorn A, Kazanc E, Ling S, Nikula C, Karali E, Paola Sera M, Vorng J, Inglese P, Maglennon G, Hamm G, Swales J, Strittmatter N, Barry ST, Sansom OJ, Poulogiannis G, Brunch J, Goodwin RJA, Takats Z (2020) Universal sample preparation unlocking multimodal molecular tissue imaging. Anal Chem 92(16):11080–11088. https://doi.org/10.1021/acs.analchem.0c00826

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work is supported by National Science Foundation (NSF) (Award# 1905335).

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Correspondence to Young-Jin Lee .

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O’Neill, K.C., Dueñas, M.E., Larson, E., Forsman, T.T., Lee, YJ. (2022). Enhancing Metabolite Coverage for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Through Multiple On-Tissue Chemical Derivatizations. In: Lee, YJ. (eds) Mass Spectrometry Imaging of Small Molecules. Methods in Molecular Biology, vol 2437. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2030-4_14

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  • DOI: https://doi.org/10.1007/978-1-0716-2030-4_14

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2029-8

  • Online ISBN: 978-1-0716-2030-4

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