Proteoform-Selective Imaging of Tissues Using Mass Spectrometry

Angew Chem Int Ed Engl. 2022 Jul 18;61(29):e202200721. doi: 10.1002/anie.202200721. Epub 2022 May 17.

Abstract

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.

Keywords: Mass Spectrometry Imaging; On-Tissue Top-down Proteomics; Post-Translational Modifications; Proteoforms.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Ions
  • Proteome / analysis
  • Proteomics / methods
  • Rats
  • Spectrometry, Mass, Electrospray Ionization* / methods
  • Tandem Mass Spectrometry* / methods

Substances

  • Ions
  • Proteome