title: Stable isotope imaging of biological samples with high resolution secondary ion mass spectrometry and complementary techniques.
abstract: Stable isotopes are ideal labels for studying biological processes because they have little or no effect on the biochemical properties of target molecules. The NanoSIMS is a tool that can image the distribution of stable isotope labels with up to 50 nm spatial resolution and with good quantitation. This combination of features has enabled several groups to undertake significant experiments on biological problems in the last decade. Combining the NanoSIMS with other imaging techniques also enables us to obtain not only chemical information but also the structural information needed to understand biological processes. This article describes the methodologies that we have developed to correlate atomic force microscopy and backscattered electron imaging with NanoSIMS experiments to illustrate the imaging of stable isotopes at molecular, cellular, and tissue scales. Our studies make it possible to address 3 biological problems: (1) the interaction of antimicrobial peptides with membranes; (2) glutamine metabolism in cancer cells; and (3) lipoprotein interactions in different tissues.
authors.affiliation: Materials Department, Oxford University, Oxford, UK. Electronic address: haibo.jiang@materials.ox.ac.uk.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: E
authors.initials: E
authors.lastname: Favaro
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Goulbourne
authors.affiliation: National Physical Laboratory, Teddington, UK; Department of Chemistry, University College London, London, UK.
authors.forename: P D
authors.initials: PD
authors.lastname: Rakowska
authors.affiliation: Materials Department, Oxford University, Oxford, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Hughes
authors.affiliation: National Physical Laboratory, Teddington, UK; School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Ryadnov
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Fong
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA; Department of Human Genetics, University of California Los Angeles, Los Angeles, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Young
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: D J P
authors.initials: DJ
authors.lastname: Ferguson
authors.affiliation: Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.affiliation: Materials Department, Oxford University, Oxford, UK.
authors.forename: C R M
authors.initials: CR
authors.lastname: Grovenor
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008074:Lipoproteins / Q000378:metabolism; D018625:Microscopy, Atomic Force / Q000379:methods*; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D023181:Antimicrobial Cationic Peptides; D008074:Lipoproteins; D005973:Glutamine
keywords: Atomic force microscopy; Backscattered electron imaging; Correlative analysis; NanoSIMS; Stable isotope