Abstract
Matrix assisted laser desorption ionisation ion mobility separation mass spectrometry imaging (MALDI-IMS-MSI) has been employed to image the distribution of proteins in ex-vivo human skin. Using a “bottom-up” proteomics approach employing “on-tissue” digestion the distribution of abundant skin proteins; collagen, keratin, decorin and serum albumin could be mapped. Images have been recorded at 150 and 30 μm spatial resolution. Multivariate statistical analysis of the data has been employed to associate specific proteins with layers of the skin. The improved specificity given by the use of ion mobility separation in mass spectrometric imaging has been demonstrated by separation of peptide ions from phospholipids.
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Jackson SN, Ugarov M, Egan T, Post JD, Langlais D, Schultz JA, Woods AS (2007) MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue. J Mass Spectrom 42:1093–1098
Giles K, Williams JP, Campuzano I (2011) Enhancements in travelling wave ion mobility resolution. Rapid Commun Mass Spectrom 25:1559–1566
Trim PJ, Henson C, Avery JL, McEwen A, Snel MF, Claude E, Marshall PM, West A, Princivalle AP, Clench MR (2008) Matrix assisted laser desorption ionisation–ion mobility separation-mass spectrometry imaging of vinblastine in whole body tissue sections. Anal Chem 80:8628–8634
Djidja MC, Francese S, Loadman PM, Sutton CW, Scriven P, Claude E, Snel MF, Franck J, Salzet M, Clench MR (2009) Detergent addition to tryptic digests and ion mobility separation prior to MS/MS improves peptide yield and protein identification for in-situ proteomic investigation of frozen and formalin-fixed paraffin-embedded adenocarcinoma tissue sections. Proteomics 9:2750–2763
Cole LM, Djidja M-C, Bluff J, Claude E, Carolan VA, Paley M, Tozer GM, Clench MR (2011) Investigation of protein induction in tumour vascular targeted strategies by MALDI-MSI. Methods 54:442–453
Djidja M-C, Claude E, Snell M, Scriven P, Francese S, Carolan VA, Clench MR (2009) MALDI-ion mobility separation-mass spectrometry imaging of glucose-regulated protein 78 kDa (Grp78) in human formalin fixed paraffin embedded pancreatic adenocarcinoma tissue sections. J Proteome Res 8:4876–4884
Djidja MC, Claude E, Snel MF, Francese S, Scriven P, Carolan V, Clench MR (2010) Novel molecular tumour classification using MALDI—mass spectrometry imaging of tissue micro-array. Anal Bioanal Chem 397:587–601
Groseclose MR, Andersson M, Hardesty WM, Caprioli RM (2007) Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry. J Mass Spectrom 42:254–262
Tornier C, Rosdy M, Maibach HI (2005) In vitro skin irritation testing on reconstituted human epidermis: reproducibility for 50 chemicals tested with two protocols. Toxicol Vitr 20:401–416
Franck J, Arafah K, Barnes A, Wisztorski M, Salzet M, Fournier I (2009) Improving tissue preparation for matrix assisted laser desorption ionisation mass spectrometry imaging. Part 1: using microspotting. Anal Chem 81:8193–8202
Trim PJ, Djidja M-C, Atkinson SJ, Oakes K, Cole LM, Anderson DMG, Hart PJ, Francese S, Clench MR (2010) A hybrid quadrupole time of flight mass spectrometer modified to incorporate a 20 kHz Nd:YVO4 laser for MALDI-MS imaging. Anal Bioanal Chem 397:3409–3419
Wong JWH, Cagney G, Cartwright HM (2005) SpecAlign—processing and alignment of mass spectra datasets. Bioinformatics 21:2088–2090
Strohalm M, Hassman M, Košata B, Kodíček M (2008) mMass Data Miner: an open source alternative for mass spectrometric data analysis. Rapid Commun Mass Spectrom 22:905–908
Strohalm M, Kavan D, Novák P, Volný M, Havlíček V (2010) mMass 3: a cross-platform software environment for precise analysis of mass spectrometric data. Anal Chem 82:4648–4651
Ivosev G, Burton L, Bonner R (2008) Dimensionality reduction and visualization in principal component analysis. Anal Chem 80:4933–4944
Balluff B, Schöne C, Höfler H, Walch A (2011) MALDI imaging mass spectrometry for direct tissue analysis: technological advancements and recent applications. Histochem Cell Biochem 136:227–244
Jurchen JC, Rubhakin SS, Sweedler JV (2005) MALDI-MS imaging of features smaller than the size of the laser beam. J Am Soc Mass Spectrom 16:1654–1659
Stauber J, MacAleese L, Franck J, Claude E, Snel M, Kaletas BK, Wiel IMVD, Wisztorski M, Fournier I, Heeren RMA (2010) On-tissue protein identification and imaging by MALDI-ion mobility mass spectrometry. J Am Soc Mass Spectrom 21:338–347
Bruand J, Sistla S, Meriaux C, Dorrestein PC, Gaasterland T, Ghassemian M, Wisztorski M, Fournier I, Salzet M, Macagno E, Bafna V (2011) Automated querying and identification of novel peptides using MALDI mass spectrometric imaging. J Proteome Res 10:1915–1928
Kallenbach M, Baldwin IT, Bonaventure G (2009) A rapid and sensitive method for the simultaneous analysis of aliphatic and polar molecules ontaining free carboxyl groups in plant extracts by LC-MS/MS. Plant Methods 5:17
Hilton GR, Thalassinos K, Grabenauer M, Sanghera N, Slade SE, Wyttenbach T, Robinson PJ, Pinheiro TJT, Bowers MT, Scrivens JH (2010) Structural analysis of prion proteins by means of drift cell and traveling wave ion mobility mass spectrometry. J Am Soc Mass Spectrom 21:845–854
Thomas A, Lenglet S, Chaurand P, Deglon J, Mangin P, Mach F, Steffens S, Wolfender J-L, Staub C (2011) Mass spectrometry for the evaluation of cardiovascular diseases based on proteomics and lipidomics. Thromb Haemost 106:20–33
Francese S, Clench MR (2010) MALDI mass spectrometry imaging, a new frontier in biostructural techniques: applications in biomedicine. In: Shah H, Garbia S (eds) Mass spectrometry for microbial proteomics. Wiley, London
Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H (2011) Keratin gene mutations in disorders of human skin and its appendages. Arch Biochem Biophys 508:123–137
Nielsen KP, Zhao L, Stamnes JJ, Stamnes K, Moan J (2008) The optics of human skin: aspects important for human health. In: Bjertness E (ed) Proceedings from the symposium “Solar Radiation and Human Health”. The Norwegian Academy of Science and Letters, Oslo, pp 35–46
Hasegawa H, Naito I, Nakano K, Momota R, Nishida K, Taguchi T, Sado Y, Ninomiya Y, Ohtsuka A (2007) The distributions of type IV collagen α chains in basement membranes of human epidermis and skin appendages. Arch Histol Cytol 70:255–265
Thrasivoulou C, Virich G, Krenacs T, Korom I, Becker DL (2011) Optical delineation of human malignant melanoma using second harmonic imaging of collagen. Biomed Opt Express 2:1282–1295
Reed CC, Iozzo RV (2003) The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconj J 19:249–255
Murphy RC, Hankin JA, Barkley RM, Zemski Berry KA (2011) MALDI imaging of lipids after matrix sublimation/deposition. Biochim Biophys Acta 1811:970–975
Jaskolla TW, Karas M, Roth U, Steinert K, Menzel C, Reihs K (2009) Comparison between vacuum sublimed matrices and conventional dried droplet preparation in MALDI-TOF mass spectrometry. J Am Soc Mass Spectrom 20:1104–1114
Bouschen W, Schulz O, Eikel D, Spengler B (2010) Matrix vapor deposition/recrystallization and dedicated spray preparation for high-resolution scanning microprobe matrix-assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS) of tissue and single cells. Rapid Commun Mass Spectrom 24:355–364
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Hart, P.J., Francese, S., Woodroofe, M.N. et al. Matrix assisted laser desorption ionisation ion mobility separation mass spectrometry imaging of ex-vivo human skin. Int. J. Ion Mobil. Spec. 16, 71–83 (2013). https://doi.org/10.1007/s12127-013-0124-6
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DOI: https://doi.org/10.1007/s12127-013-0124-6