Native mass spectrometry imaging of proteins and protein complexes by nano-DESI

Oliver Hale; Helen Cooper

doi:10.1021/acs.analchem.0c05277

Native mass spectrometry imaging of proteins and protein complexes by nano-DESI

Oliver Hale, Helen Cooper

Biosciences

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Abstract

Previously, we have demonstrated native mass spectrometry imaging (native MSI) in which the spatial distribution of proteins maintained in their native-like, folded conformations was determined using liquid extraction surface analysis (LESA). While providing an excellent testbed for proof of principle, the spatial resolution of LESA is currently limited for imaging primarily by the physical size of the sampling pipette tip. Here, we report the adoption of nanospray-desorption electrospray ionization (nano-DESI) for native MSI, delivering substantial improvements in resolution versus native LESA MSI. In addition, native nano-DESI may be used for location-targeted top-down proteomics analysis directly from tissue. Proteins, including a homodimeric complex not previously detected by native MSI, were identified through a combination of collisional activation, high-resolution MS and proton transfer charge reduction.

Original language	English
Pages (from-to)	4619–4627
Number of pages	9
Journal	Analytical Chemistry
Volume	93
Issue number	10
Early online date	4 Mar 2021
DOIs	https://doi.org/10.1021/acs.analchem.0c05277
Publication status	Published - 16 Mar 2021

Bibliographical note

Funding Information: H.J.C. is an EPSRC Established Career Fellow (EP/S002979/1). O.J.H. is funded by EPSRC (EP/S002979/1). The Orbitrap Eclipse mass spectrometer used in this work was funded by BBSRC (BB/S019456/1).

ASJC Scopus subject areas

Analytical Chemistry

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10.1021/acs.analchem.0c05277Licence: Creative Commons: Attribution (CC BY)

HaleO2021NativeFinal published version, 6.42 MBLicence: Creative Commons: Attribution (CC BY)

A new mass spectrometer for structural proteomics and protein imaging
Thomas, C. (Co-Investigator), Grant, M. (Co-Investigator), Lovering, A. (Co-Investigator), Alderwick, L. (Co-Investigator), Tomlinson, M. (Co-Investigator), Winn, P. (Co-Investigator), Knowles, T. (Co-Investigator), Cooper, H. (Principal Investigator), Styles, I. (Co-Investigator), Gibbs, D. (Co-Investigator), Huber, D. (Co-Investigator), Bhatt, A. (Co-Investigator) & Leney, A. (Co-Investigator)
Biotechnology & Biological Sciences Research Council
1/07/19 → 30/06/20
Project: Research
NAMS: Native ambient mass spectrometry
Cooper, H. (Principal Investigator)
Engineering & Physical Science Research Council
1/06/19 → 30/11/23
Project: Research

Cite this

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title = "Native mass spectrometry imaging of proteins and protein complexes by nano-DESI",

abstract = "Previously, we have demonstrated native mass spectrometry imaging (native MSI) in which the spatial distribution of proteins maintained in their native-like, folded conformations was determined using liquid extraction surface analysis (LESA). While providing an excellent testbed for proof of principle, the spatial resolution of LESA is currently limited for imaging primarily by the physical size of the sampling pipette tip. Here, we report the adoption of nanospray-desorption electrospray ionization (nano-DESI) for native MSI, delivering substantial improvements in resolution versus native LESA MSI. In addition, native nano-DESI may be used for location-targeted top-down proteomics analysis directly from tissue. Proteins, including a homodimeric complex not previously detected by native MSI, were identified through a combination of collisional activation, high-resolution MS and proton transfer charge reduction.",

author = "Oliver Hale and Helen Cooper",

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Native mass spectrometry imaging of proteins and protein complexes by nano-DESI

Abstract

Bibliographical note

ASJC Scopus subject areas

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Projects

A new mass spectrometer for structural proteomics and protein imaging

NAMS: Native ambient mass spectrometry

Cite this