Qi Chengjian, Li Xiaoni, Li Qian, Shi Xiujuan, Xia Meng-Chan, Chen Yanhua, Wang Zhaoying, Abliz Zeper
Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), State Ethnic Affairs Commission, Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China.
Key Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Minzu University of China, Beijing 100081, China.
Anal Chem. 2024 Sep 13. doi: 10.1021/acs.analchem.4c03679.
Unsaturated lipids with carbon-carbon double bonds (C═C) have been implicated in the pathogenesis of various diseases. While mass spectrometry imaging (MSI) has been employed to map the distribution of lipid isomers in tissue sections, the identification of lipid C═C positional isomers at the single-cell level using MSI poses a significant challenge. In this study, we developed a novel approach utilizing ToF-SIMS in conjunction with the Paternò-Büchi (P-B) photochemical reaction to characterize the C═C localization in unsaturated lipid isomers at the single-cell level. The P-B reaction was employed to produce adduct products, which were subsequently subjected to collision-induced dissociation by the primary ion beam of ToF-SIMS to generate characteristic ion pairs indicative of the presence of C═C bonds. Utilizing this approach, lipid isomers in brain and skeletal tissues from mice, as well as different cell lines, were visualized at single-cell resolution. Furthermore, distinct variations in the composition of FA 18:1 isomers across different microregions and cell types were revealed. Our P-B ToF-SIMS approach enables the accurate identification and characterization of complex lipid structures with remarkable spatial resolution and can be helpful in understanding the physiological role of these C═C positional isomers.
含有碳 - 碳双键（C═C）的不饱和脂质与多种疾病的发病机制有关。虽然质谱成像（MSI）已被用于绘制组织切片中脂质异构体的分布，但使用MSI在单细胞水平上鉴定脂质C═C位置异构体面临重大挑战。在本研究中，我们开发了一种新方法，利用飞行时间二次离子质谱（ToF-SIMS）结合帕特诺 - 布齐（P-B）光化学反应，在单细胞水平上表征不饱和脂质异构体中C═C的定位。P-B反应用于产生加合物产物，随后通过ToF-SIMS的一次离子束对其进行碰撞诱导解离，以生成指示C═C键存在的特征离子对。利用这种方法，在小鼠的脑和骨骼肌组织以及不同细胞系中的脂质异构体以单细胞分辨率进行了可视化。此外，还揭示了不同微区和细胞类型中FA 18:1异构体组成的明显差异。我们的P-B ToF-SIMS方法能够以卓越的空间分辨率准确鉴定和表征复杂的脂质结构，并有助于理解这些C═C位置异构体的生理作用。
