Proteoform-Selective Imaging of Tissues Using Mass Spectrometry.
Manxi YangHang HuPei SuPaul M ThomasJeannie M CamarilloJoseph B GreerBryan P EarlyRyan T FellersNeil L KelleherJulia LaskinPublished in: Angewandte Chemie (International ed. in English) (2022)
Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform-specific analysis of the proteome. Herein, we employ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) for the proteoform-selective imaging of biological tissues. Nano-DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS) directly on the tissue. Proof-of-concept experiments demonstrate that nano-DESI MSI combined with on-tissue top-down proteomics is ideally suited for the proteoform-selective imaging of tissue sections. Using rat brain tissue as a model system, we provide the first evidence of differential proteoform expression in different regions of the brain.
Keyphrases
- high resolution
- mass spectrometry
- liquid chromatography
- tandem mass spectrometry
- high performance liquid chromatography
- gas chromatography
- gene expression
- simultaneous determination
- white matter
- small molecule
- fluorescence imaging
- brain injury
- quantum dots
- photodynamic therapy
- capillary electrophoresis
- water soluble