Abstract
Imaging mass spectrometry (IMS) is a useful cutting edge technology used to investigate the distribution of biomolecules such as drugs and metabolites, as well as to identify molecular species in tissues and cells without labeling. To protect against excess water loss that is essential for survival in a terrestrial environment, mammalian skin possesses a competent permeability barrier in the stratum corneum (SC), the outermost layer of the epidermis. The key lipids constituting this barrier in the SC are the ceramides (Cers) comprising of a heterogeneous molecular species. Alterations in Cer composition have been reported in several skin diseases that display abnormalities in the epidermal permeability barrier function. Not only the amounts of different Cers, but also their localizations are critical for the barrier function. We have employed our new imaging system, capable of high-lateral-resolution IMS with an atmospheric-pressure ionization source, to directly visualize the distribution of Cers. Moreover, we show an ichthyotic disease pathogenesis due to abnormal Cer metabolism in Dorfman–Chanarin syndrome, a neutral lipid storage disorder with ichthyosis in human skin, demonstrating that IMS is a novel diagnostic approach for assessing lipid abnormalities in clinical setting, as well as for investigating physiological roles of lipids in cells/tissues.
Highlights
Imaging mass spectrometry (IMS) has several advantages for exploring the two-dimensional distribution of lipids [1,2,3]: First, IMS does not require any labels or specific probes to investigate the localization; second, IMS is a non-targeted imaging method, allowing us to detect the localization of unexpected metabolites [4,5,6,7]
Signal intensity of Cer-related ions by vacuumtype matrix-assisted laser desorption/ionization (MALDI) instrument was higher than the AP ion-source instrument, there is no significant difference of a signal-to-noise (S/N) ratio between the two instruments
Subsequent tandem mass spectrometric analysis revealed the generation of stable product ions with m/z 282.3 and 264.3 corresponding to the loss of an amide-bound acyl group and one or two molecules of water, respectively [33] (Fig. 2e), indicating that the signal at m/z 632.5 detected on the brain tissue is a Cer molecule
Summary
Imaging mass spectrometry (IMS) has several advantages for exploring the two-dimensional distribution of lipids [1,2,3]: First, IMS does not require any labels or specific probes to investigate the localization; second, IMS is a non-targeted imaging method, allowing us to detect the localization of unexpected metabolites [4,5,6,7]. IMS has been applied to lipid imaging analysis because lipids have relatively small molecular sizes compared to proteins/peptides and lack specific probes for other imaging techniques. The recent experimental model of IMS demonstrates the highest resolution (,1 mm) [10], while conventional matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometers are equipped with lasers of diameter 10–100 mm [11,12,13,14]. Using a 10-mmdiameter laser, the instrument can visualize the distribution of biomolecules, including volatile molecules. Since this machine employs an AP ion-source chamber that utilizes soft ionization and a QIT that concentrates the specific ions to be analyzed, we hypothesize that ion suppression of Cers from other lipids is avoided in this case
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