Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag.

Taiga Iwama, Kuniyuki Kano, Daisuke Saigusa, Kim Ekroos, Gerhild van Echten-Deckert, Johannes Vogt, Junken Aoki

Analytical chemistry 2021 Mar 02

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Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is an emerging label-free method for mapping the distribution of diverse molecular species in tissue sections. Despite recent progress in MALDI-MSI analyses of lipids, it is still difficult to visualize minor bioactive lipids including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Here, we have developed a novel on-tissue derivatization method using Phos-tag, a zinc complex that specifically binds to a phosphate monoester group. MALDI-MSI with Phos-tag derivatization made it possible to image LPA and S1P in the murine brain. Furthermore, we were able to visualize other low-abundance lipids containing phosphate monoester, such as phosphatidic acid and ceramide-1-phosphate. Compared with conventional MALDI-MS, this derivatization produced LPA images with high spatial accuracy discriminating LPA artificially produced during MALDI-MS analysis. In mice with deficiencies in enzymes that degrade LPA and S1P, we observed marked S1P and/or LPA accumulation in specific regions of the brain. Thus, the present study provides a simple and optimal way to reveal the spatial localization of potent bioactive lipid phosphates such as LPA and S1P in tissues.

Citation

Taiga Iwama, Kuniyuki Kano, Daisuke Saigusa, Kim Ekroos, Gerhild van Echten-Deckert, Johannes Vogt, Junken Aoki. Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag. Analytical chemistry. 2021 Mar 02;93(8):3867-3875