Multiplexed imaging mass spectrometry of the extracellular matrix using serial enzyme digests from formalin-fixed paraffin-embedded tissue sections.

Analytical and Bioanalytical Chemistry
Cassandra L CliftPeggi M Angel

Abstract

We report a multiplexed imaging mass spectrometry method which spatially localizes and selectively accesses the extracellular matrix on formalin-fixed paraffin-embedded tissue sections. The extracellular matrix (ECM) consists of (1) fibrous proteins, post-translationally modified (PTM) via N- and O-linked glycosylation, as well as hydroxylation on prolines and lysines, and (2) glycosaminoglycan-decorated proteoglycans. Accessing all these components poses a unique analytical challenge. Conventional peptide analysis via trypsin inefficiently captures ECM peptides due to their low abundance, intra- and intermolecular cross-linking, and PTMs. In previous studies, we have developed matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) techniques to capture collagen peptides via collagenase type III digestion, both alone and after N-glycan removal via PNGaseF digest. However, in fibrotic tissues, the buildup of ECM components other than collagen-type proteins, including elastin and glycosaminoglycans, limits efficacy of any single enzyme to access the complex ECM. Here, we have developed a novel serial enzyme strategy to define the extracellular matrix, including PTMs, from a single tissue section for MAL...Continue Reading

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Citations

Jun 16, 2021·Expert Review of Proteomics·Peggi M AngelRichard Drake
Aug 10, 2021·Frontiers in Chemistry·Dylan Nicholas TabangLingjun Li
Aug 16, 2021·Mass Spectrometry Reviews·Colin T McDowellRichard R Drake
Sep 11, 2021·Electrophoresis·Kaitlyn B DonohooYehia Mechref
Oct 30, 2021·Journal of the American Society for Mass Spectrometry·Cassandra L CliftPeggi M Angel

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