Imaging of Membrane Lipids in Single Cells by Imprint-Imaging Time-of-Flight Secondary Ion Mass Spectrometry

Sjövall, Peter; Lausmaa, Jukka; Nygren, Håkan; Carlsson, Lennart; Malmberg, Per

doi:10.1021/ac0207675

Cited by 145 publications

(110 citation statements)

References 19 publications

(31 reference statements)

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“…In comparison to the silver imprint technique used previously [14], the silver coating technique offers several significant advantages. The silver imprint technique produces a layer of organic material, on the silver matrix, that varies in thickness over the surface.…”

Section: Discussionmentioning

confidence: 99%

Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections

Nygren¹,

Malmberg²,

Kriegeskotte³

et al. 2004

FEBS Letters

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106

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Here, we show the localization of a whole organic molecule in biological tissue using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Rat kidneys were sectioned by cryoultramicrotomy and dried at room temperature. The samples were covered with a thin silver layer and analyzed in an imaging TOF-SIMS instrument equipped with a Ga þ -source. The cholesterol signal showed a high concentration in the nuclear areas of the epithelial cells and a lower concentration over areas representing the basal lamina of renal tubules. A more diffuse distribution of cholesterol was also found over areas representing the cytoplasm or plasma membrane of the epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections

Nygren¹,

Malmberg²,

Kriegeskotte³

et al. 2004

FEBS Letters

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106

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“…PC fragments and cholesterol have been found to have a complementary distribution in the rat cerebellum (26) and in capillary blood leukocytes (41). Cholesteryl sulfate ions have been identified in ToF-SIMS imaging of human skin and renal human samples from a patient with a genetic disease (16).…”

Section: Pc Cholesterol and Sm Colocalizationmentioning

confidence: 99%

Lipid mapping in human dystrophic muscle by cluster-time-of-flight secondary ion mass spectrometry imaging

Tahallah

Brunelle

Porte

et al. 2008

Journal of Lipid Research

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Human striated muscle samples, from male control and Duchenne muscular dystrophy-affected children, were subjected to cluster-time-of-flight secondary ion mass spectrometry (cluster-ToF-SIMS) imaging using a 25 keV Bi 3 1 liquid metal ion gun under static SIMS conditions. Spectra and ion density maps, or secondary ion images, were acquired in both positive and negative ion mode over several areas of 500 3 500 mm 2 (image resolution, 256 3 256 pixels). Characteristic distributions of various lipids were observed. Vitamin E and phosphatidylinositols were found to concentrate within the cells, whereas intact phosphocholines accumulated over the most damaged areas of the dystrophic muscles, together with cholesterol and sphingomyelin species. Fatty acyl chain composition varied depending on the region, allowing estimation of the local damage extent.-Tahallah, N., A. Brunelle, S. De La Porte, and O. Laprévote. Lipid mapping in human dystrophic muscle by cluster-time-of-flight secondary ion mass spectrometry imaging. J. Lipid Res. 2008. 49: 438-454.

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“…Moreover, this technique provides a high rate of fragmentation, which can be used for the identification of ions by structural analysis. To our knowledge, only brain sections (14,15) and single cells (16) have been analyzed by TOF-SIMS and cluster TOF-SIMS imaging, and no study linked to a molecular disease has been developed with this method.…”

Section: Supplementary Abstract Colocalization • Oxidative Stress • mentioning

confidence: 99%

Lipid imaging by gold cluster time-of-flight secondary ion mass spectrometry: application to Duchenne muscular dystrophy

Touboul

Brunelle

Halgand

et al. 2005

Journal of Lipid Research

122

120

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Imaging with time-of-flight secondary ion mass spectrometry (TOF-SIMS) has expanded very rapidly with the development of gold cluster ion sources (Au 3 ؉ ). It is now possible to acquire ion density maps (ion images) on a tissue section without any treatment and with a lateral resolution of few micrometers. In this article, we have taken advantage of this technique to study the degeneration/regeneration process in muscles of a Duchenne muscular dystrophy model mouse. Specific distribution of different lipid classes (fatty acids, triglycerides, phospholipids, tocopherol, coenzyme Q9, and cholesterol) allows us to distinguish three different regions on a mouse leg section: one is destroyed, another is degenerating (oxidative stress and deregulation of the phosphoinositol cycle), and the last one is stable. TOF-SIMS imaging shows the ability to localize directly on a tissue section a great number of lipid compounds that reflect the state of the cellular metabolism. In lipidomics, as in all biological domains, the simultaneous localization of numerous organic compounds in tissue sections is a crucial issue for understanding cellular metabolic processes. New tools are developed to acquire the maximum amount of data in a short time, and the use of mass spectrometry images to manage information on biological tissue surfaces is increasing rapidly.Two mass spectrometry imaging methods have been developed. The first one is based on matrix-assisted laser desorption ionization (MALDI) (1, 2) coupled with a timeof-flight (TOF) technique, which leads to the acquisition of images in a mass range from 500 to a few tens of thousands daltons with a spatial resolution of ‫ف‬ 50 m (3, 4), and the second one is based on TOF secondary ion mass spectrometry (SIMS), which leads to the acquisition of images with masses of Ͻ 1,000 Da with a spatial resolution of 1 m or less (5-7). In both cases, tissue sections having a thickness of 10-20 m are cut using a cryostat at Ϫ 20 Њ C and transferred to target plates (stainless steel or glass). For MALDI-TOF experiments, the matrix is deposited by air spray, whereas no preliminary sample coating is needed for TOF-SIMS experiments. A laser (MALDI) or a focused ion beam (SIMS), both pulsed, irradiates the sample at each surface element, which is called a spot, and from which a mass spectrum is acquired and recorded. Each spot corresponds to a pixel of the image, and the intervals between each spot define the lateral resolution. The inevitable use of a matrix could be a weakness of the MALDI technique: homogeneous deposition by air spray is difficult to control, and the signal visibility is low for m/z Ͻ 600 because of mass interference with matrix ion peaks (8). Tandem mass spectrometry imaging experiments can extend the accessible mass range down to m/z ‫ف‬ 100-200, but to the detriment of the spatial resolution, which is only 500 m with present tandem mass spectrometers (9). Future improvements are expected toward a better spatial resolution of 1-10 m in association with reasonable data...

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Imaging of Membrane Lipids in Single Cells by Imprint-Imaging Time-of-Flight Secondary Ion Mass Spectrometry

Cited by 145 publications

References 19 publications

Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections

Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections

Lipid mapping in human dystrophic muscle by cluster-time-of-flight secondary ion mass spectrometry imaging

Lipid imaging by gold cluster time-of-flight secondary ion mass spectrometry: application to Duchenne muscular dystrophy

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