Analytical Chemistry

Proteoform-selective imaging of tissues using mass spectrometry

Authors

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.

Version notes

The manuscript was polished and proteoform assignments were updated.

Content

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Supplementary material

Thumbnail image of Supporting Information.pdf
Supporting information
This document contains the descriptions of methods and experiments, and supplemental figures.
Thumbnail image of Supporting Table.xlsx
Supporting table
This document contains the proteoforms assignments.