Native Mass Spectrometry Imaging of Proteins and Protein Complexes by Nano-DESI

Hale, Oliver J.; Cooper, Helen J.

doi:10.1021/acs.analchem.0c05277

Cited by 94 publications

(122 citation statements)

References 45 publications

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“…proteoforms [71]), such as in rat brain region microenvironments [72]. Advances in mass spectrometry ionization techniques [73,74] and gas-phase separation [75] have improved detection proteins by MSI, and new software has made processing and statistical analysis more accessible [76,77].…”

Section: Mass Spectrometry Imagingmentioning

confidence: 99%

Proximity labeling and other novel mass spectrometric approaches for spatiotemporal protein dynamics

Pino

Schilling

2021

Expert Review of Proteomics

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Background: Proteins are highly dynamic and their biological function is controlled by not only temporal abundance changes but also via regulated protein-protein interaction networks, which respond to internal and external perturbations. A wealth of novel analytical reagents and workflows allow studying spatiotemporal protein environments with great granularity while maintaining high throughput and ease of analysis. Areas covered: We review technology advances for measuring protein-protein proximity interactions with an emphasis on proximity labeling, and briefly summarize other spatiotemporal approaches including protein localization, and their dynamic changes over time, specifically in human cells and mammalian tissues. We focus especially on novel technologies and workflows emerging within the past 5 years. This includes enrichment-based techniques (proximity labeling and crosslinking), separationbased techniques (organelle fractionation and size exclusion chromatography), and finally sortingbased techniques (laser capture microdissection and mass spectrometry imaging). Expert opinion: Spatiotemporal proteomics is a key step in assessing biological complexity, understanding refined regulatory mechanisms, and forming protein complexes and networks. Studying protein dynamics across space and time holds promise for gaining deep insights into how protein networks may be perturbed during disease and aging processes, and offer potential avenues for therapeutic interventions, drug discovery, and biomarker development.

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Section: Mass Spectrometry Imagingmentioning

confidence: 99%

Proximity labeling and other novel mass spectrometric approaches for spatiotemporal protein dynamics

Pino

Schilling

2021

Expert Review of Proteomics

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“…One major challenge in proteoform imaging using liquid extraction-based techniques is the detection of low-abundance, high mass proteoforms in the congested MS spectra produced by ionizing complex mixtures of biomolecules extracted from the sample. Until now, imaging and identification of intact proteoforms directly from tissue has been limited to <20 kDa species (27,28,32,33), with one report leading to the identification of subunits from a 43 kDa trimeric protein complex (34). Here, we address this challenge using individual ion mass spectrometry (I 2 MS).…”

Section: Introductionmentioning

confidence: 99%

Direct Imaging and Identification of Proteoforms up to 70 kDa from Human Tissue

McGee

Durbin

et al. 2021

Preprint

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Imaging of proteoforms in human tissues is hindered by low molecular specificity and limited proteome coverage. Here, we introduce proteoform imaging mass spectrometry (PiMS), which increases the size limit for proteoform detection and identification by 4-fold compared to reported methods, and reveals tissue localization of proteoforms at <80 μm spatial resolution. PiMS advances proteoform imaging by combining liquid sampling (nanospray desorption electrospray ionization, nano-DESI) with ion detection using individual ion mass spectrometry (I2MS). We demonstrate the first proteoform imaging of human kidney, identifying 169 of 400 proteoforms <70 kDa using top-down mass spectrometry and database lookup from the human proteoform atlas, including dozens of key enzymes in primary metabolism. Moreover, PiMS images visualize kidney anatomical structures and cellular neighborhoods in the vasculature versus the medulla or the cortex. The benefits of PiMS are poised to increase proteome coverage for label-free protein imaging of intact tissues.

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“…30 By virtue of the excellent desorption capability, this ionization technique also allowed direct detection and MS imaging of typical proteins in tissue sections. [31][32][33] Despite these advances, selectively measuring low-abundance proteins/peptides of pathological significance from the complexity of biosamples by AIMS in a sensitive and quantitative fashion remains challenging.…”

Section: Introductionmentioning

confidence: 99%