Abstract
Imaging mass spectrometry (IMS) is two-dimensional mass spectrometry to visualize the spatial distribution of biomolecules, which does not need either separation or purification of target molecules, and enables us to monitor not only the identification of unknown molecules but also the localization of numerous molecules simultaneously. Among the ionization techniques, matrix assisted laser desorption/ionization (MALDI) is one of the most generally used for IMS, which allows the analysis of numerous biomolecules ranging over wide molecular weights. Proper selection and preparation of matrix is essential for successful imaging using IMS. Tandem mass spectrometry, which is referred to MSn, enables the structural analysis of a molecule detected by the first step of IMS. Applications of IMS were initially developed for studying proteins or peptides. At present, however, targets of IMS research have expanded to the imaging of small endogenous metabolites such as lipids, exogenous drug pharmacokinetics, exploring new disease markers, and other new scientific fields. We hope that this new technology will open a new era for biophysics.
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References
Altelaar AF, Taban IM, McDonnell LA, Verhaert PDEM, de Lange RP, Adan RAH, Mooi WJ, Heeren RM, Piersma SR (2007) High-resolution MALDI imaging mass spectrometry allows localization of peptide distributions at cellular length scales in pituitary tissue sections. Int J Mass Spectrom 260:293–211. doi:10.1016/j.ijms.2006.09.028
Atkinson SJ, Loadman PM, Sutton C, Patterson LH, Clench MR (2007) Examination of the distribution of the bioreductive drug AQ4N and its active metabolite AQ4 in solid tumours by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom 21:1271–1276. doi:10.1002/rcm.2952
Aveldano MI (1988) Phospholipid species containing long and very long polyenoic fatty acids remain with rhodopsin after hexane extraction of photoreceptor membranes. Biochemistry 27:1229–1239. doi:10.1021/bi00404a024
Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69:4751–4760. doi:10.1021/ac970888i
Chaurand P, Stoeckli M, Caprioli RM (1999) Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. Anal Chem 71:5263–5270. doi:10.1021/ac990781q
Chaurand P, Schwartz SA, Billheimer D, Xu BJ, Crecelius A, Caprioli RM (2004) Integrating histology and imaging mass spectrometry. Anal Chem 76:1145–1155. doi:10.1021/ac0351264
Chaurand P, Norris JL, Cornett DS, Mobley JA, Caprioli RM (2006) New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. J Proteome Res 5:2889–2900. doi:10.1021/pr060346u
Cornett DS, Mobley JA, Dias EC, Andersson M, Arteaga CL, Sanders ME, Caprioli RM (2006) A novel histology-directed strategy for MALDI-MS tissue profiling that improves throughput and cellular specificity in human breast cancer. Mol Cell Proteomics 5:1975–1983. doi:M600119-MCP200
Denkert C, Budczies J, Kind T, Weichert W, Tablack P, Sehouli J, Niesporek S, Konsgen D, Dietel M, Fiehn O (2006) Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors. Cancer Res 66:10795–10804. doi:66/22/10795
Ford DA, Monda JK, Brush RS, Anderson RE, Richards MJ, Fliesler SJ (2008) Lipidomic analysis of the retina in a rat model of Smith-Lemli-Opitz syndrome: alterations in docosahexaenoic acid content of phospholipid molecular species. J Neurochem 105:1032–1047. doi:JNC5203
Garrett TJ, Prieto-Conaway MC, Kovtoun V, Bui H, Izgarian N, Stafford G, Yost RA (2006) Imaging of small molecules in tissue sections with a new intermediate-pressure MALDI linear ion trap mass spectrometer. Int J Mass Spectrom 260:166–176. doi:10.1016/j.ijms.2006.09.019
Goto-Inoue N, Hayasaka T, Sugiura Y, Taki T, Li YT, Matsumoto M, Setou M (2008) High-sensitivity analysis of glycosphingolipids by matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight imaging mass spectrometry on transfer membranes. J Chromatogr B Analyt Technol Biomed Life Sci 870:74–83. doi:S1570-0232(08)00395-4
Hannun YA, Bell RM (1989) Functions of sphingolipids and sphingolipid breakdown products in cellular regulation. Science 243:500–507. doi:10.1126/science.2643164
Hatanaka T, Hatanaka Y, Tsuchida J, Ganapathy V, Setou M (2006) Amino acid transporter ATA2 is stored at the trans-Golgi network and released by insulin stimulus in adipocytes. J Biol Chem 281:39273–39284. doi:M604534200
Hayasaka T, Goto-Inoue N, Sugiura Y, Zaima N, Nakanishi H, Ohishi K, Nakanishi S, Naito T, Taguchi R, Setou M (2008) Matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)-based imaging mass spectrometry reveals a layered distribution of phospholipid molecular species in the mouse retina. Rapid Commun Mass Spectrom 22:3415–3426. doi:10.1002/rcm.3751
Ikegami K, Setou M (2009) TTLL10 can perform tubulin glycylation when co-expressed with TTLL8. FEBS Lett 583:1957–1963. doi:10.1016/j.febslet.2009.05.003
Ikegami K, Heier RL, Taruishi M, Takagi H, Mukai M, Shimma S, Taira S, Hatanaka K, Morone N, Yao I, Campbell PK, Yuasa S, Janke C, Macgregor GR, Setou M (2007) Loss of α-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function. Proc Natl Acad Sci USA 104:3213–3218. doi:10.1073/pnas.0611547104
Ikegami K, Horigome D, Mukai M, Livnat I, MacGregor GR, Setou M (2008) TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1. FEBS Lett 582:1129–1134. doi:S0014-5793(08)00202-0
Jackson SN, Wang HY, Woods AS (2005) Direct profiling of lipid distribution in brain tissue using MALDI-TOFMS. Anal Chem 77:4523–4527. doi:10.1021/ac050276v
Jackson SN, Ugarov M, Egan T, Post JD, Langlais D, Albert Schultz J, Woods AS (2007) MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue. J Mass Spectrom 42:1093–1098. doi:10.1002/jms.1245
Kahyo T, Mostoslavsky R, Goto M, Setou M (2008) Sirtuin-mediated deacetylation pathway stabilizes Werner syndrome protein. FEBS Lett 582:2479–2483. doi:S0014-5793(08)00542-5
Karas M, Hillenkamp F (1988) Laser desorption ionization of proteins with molecular masses exceeding 10, 000 daltons. Anal Chem 60:2299–2301. doi:10.1021/ac00171a028
Khatib-Shahidi S, Andersson M, Herman JL, Gillespie TA, Caprioli RM (2006) Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. Anal Chem 78:6448–6456. doi:10.1021/ac060788p
Konishi Y, Setou M (2009) Tubulin tyrosination navigates the kinesin-1 motor domain to axons. Nat Neurosci 12:559–567. doi:nn.2314
Lapolla A, Ragazzi E, Andretta B, Fedele D, Tubaro M, Seraglia R, Molin L, Traldi P (2007) Multivariate analysis of matrix-assisted laser desorption/ionization mass spectrometric data related to glycoxidation products of human globins in nephropathic patients. J Am Soc Mass Spectrom 18:1018–1023. doi:S1044-0305(07)00140-7
McCombie G, Staab D, Stoeckli M, Knochenmuss R (2005) Spatial and spectral correlations in MALDI mass spectrometry images by clustering and multivariate analysis. Anal Chem 77:6118–6124. doi:10.1021/ac051081q
Pan HZ, Zhang H, Chang D, Li H, Sui H (2008) The change of oxidative stress products in diabetes mellitus and diabetic retinopathy. Br J Ophthalmol 92:548–551. doi:92/4/548
Puolitaival SM, Burnum KE, Cornett DS, Caprioli RM (2008) Solvent-free matrix dry-coating for MALDI imaging of phospholipids. J Am Soc Mass Spectrom 19:882–886. doi:S1044-0305(08)00119-0
Schwartz SA, Weil RJ, Thompson RC, Shyr Y, Moore JH, Toms SA, Johnson MD, Caprioli RM (2005) Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry. Cancer Res 65:7674–7681. doi:65/17/7674
Setou M, Matsumoto M, Hosokawa N, Sugiura Y, Hayasaka T (2008a) Development of mass microscopy. Microscope 43:24–28
Setou M, Hayasaka T, Shimma S, Sugiura Y, Matsumoto M (2008b) Protein denaturation improves enzymatic digestion efficiency for direct tissue analysis using mass spectrometry. Appl Surf Sci 255:1555–1559. doi:10.1016/j.apsusc.2008.05.120
Shimma S, Setou M (2007) Mass microscopy to reveal distinct localization of Heme B (m/z 616) in colon cancer liver metastasis. J Mass Spectrom Soc Jpn 55:230–238
Shimma S, Furuta M, Ichimura K, Yoshida Y, Setou M (2006a) A novel approach to in situ proteome analysis using chemical inkjet printing technology and MALDI-QIT-TOF tandem mass spectrometer. J Mass Spectrom Soc Jpn 54:133–140
Shimma S, Furuta M, Ichimura K, Yoshida Y, Setou M (2006b) Direct MS/MS analysis in mammalian tissue sections using MALDI-QIT-TOFMS and chemical inkjet technology. Surf Int Anal 38:1712–1714. doi:10.1002/sia.2389
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 Analyt Technol Biomed Life Sci 855:98–103. doi:10.1016/j.jchromb.2007.02.037
Shimma S, Sugiura Y, Hayasaka T, Zaima N, Matsumoto M, Setou M (2008) Mass imaging and identification of biomolecules with MALDI-QIT-TOF-based system. Anal Chem 80:878–885. doi:10.1021/ac071301v
Skold K, Svensson M, Nilsson A, Zhang X, Nydahl K, Caprioli RM, Svenningsson P, Andren PE (2006) Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. J Proteome Res 5:262–269. doi:10.1021/pr050281f
Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7:493–496. doi:10.1038/86573
Stoeckli M, Staab D, Staufenbiel M, Wiederhold KH, Signor L (2002) Molecular imaging of amyloid beta peptides in mouse brain sections using mass spectrometry. Anal Biochem 311:33–39. doi:10.1016/S0003-2697(02)00386-X
Stoeckli M, Staab D, Schweitzer A (2006) Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole body tissue sections. Int J Mass Spectrom 260:195–202. doi:10.1016/j.ijms.2006.10.007
Sugiura Y, Shimma S, Setou M (2006a) Thin sectioning improves the peak intensity and signal-to-noise ratio in direct tissue mass spectrometry. J Mass Spectrom Soc Jpn 54:45–48
Sugiura Y, Shimma S, Setou M (2006b) Two-step matrix application technique to improve ionization efficiency for matrix-assisted laser desorption/ionization in imaging mass spectrometry. Anal Chem 78:8227–8235. doi:10.1021/ac060974v
Sugiura Y, Shimma S, Konishi Y, Yamada MK, Setou M (2008) Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglioside molecular species in the mouse hippocampus. PLoS ONE 3:e3232. doi:10.1371/journal.pone.0003232
Sugiura Y, Konishi Y, Zaima N, Kajihara S, Nakanishi H, Taguchi R, Setou M (2009) Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry. J Lipid Res (in press)
Suzuki M, Kamei M, Itabe H, Yoneda K, Bando H, Kume N, Tano Y (2007) Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration. Mol Vis 13:772–778. doi:v13/a84
Taira S, Sugiura Y, Moritake S, Shimma S, Ichiyanagi Y, Setou M (2008) Nanoparticle-assisted laser desorption/ionization based mass imaging with cellular resolution. Anal Chem 80:4761–4766. doi:10.1021/ac800081z
Yao I, Takagi H, Ageta H, Kahyo T, Sato S, Hatanaka K, Fukuda Y, Chiba T, Morone N, Yuasa S, Inokuchi K, Ohtsuka T, Macgregor GR, Tanaka K, Setou M (2007) SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell 130:943–957. doi:S0092-8674(07)00902-6
Yao I, Sugiura Y, Matsumoto M, Setou M (2008) In situ proteomics with imaging mass spectrometry and principal component analysis in the Scrapper-knockout mouse brain. Proteomics 8:3692–3701. doi:10.1002/pmic.200701121
Zaima N, Hayasaka T, Goto-Inoue N, Setou M (2009a) Imaging of metabolites by MALDI mass spectrometry. J Oleo Sci 58:415–419
Zaima N, Matsuyama Y, Setou M (2009b) Principal component analysis of direct matrix-assisted laser desorption/ionization mass spectrometric data related to metabolites of fatty liver. J Oleo Sci 58:267–273
Acknowledgements
We are grateful to our collaborators in the Hamamatsu University School of Medicine—Dr. S. Koizumi, Dr. T. Hayasaka, Dr. N. Goto-Inoue, Dr. I. Yao, Dr. N. Zaima, Dr. K. Ikegami, Dr. H. Tanaka, and Dr. Y. Morita. This work was supported by a Grant-in-Aid for SENTAN from the Japanese Science and Technology Agency (JST) and Young Scientists S (2067004) by Japan Society for the Promotion of Science (JSPS) to Mitsutoshi Setou.
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Murayama, C., Kimura, Y. & Setou, M. Imaging mass spectrometry: principle and application. Biophys Rev 1, 131–139 (2009). https://doi.org/10.1007/s12551-009-0015-6
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DOI: https://doi.org/10.1007/s12551-009-0015-6