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New Insights on Mass Spectometry Applied to Bioscience

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 23614

Special Issue Editors


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Guest Editor
Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
Interests: proteomes; cancers

E-Mail Website
Guest Editor
Department Oncology, Faculty of Medicine, McGill University, Montreal, QC H3G 1Y6, Canada
Interests: proteomics; biomarkers; metabolomics; structural proteomics; clinical diagnostics

Special Issue Information

This Special Issue will contain manuscripts on the latest mass spectrometry-based technologies and techniques, including newly developed approaches and methods applied to bioscience. Both reviews and original articles on novel instrumental mass spectrometric approaches in biosciences, quantitative proteomics, and single-cell proteomics will be included. Of particular interest are approaches which can provide highly multiplexed protein quantitation with rapid analysis times. 

This issue will also contain articles on the latest developments in peptide and protein imaging, novel methods in structural proteomics, proteogenomics, and proteomulti-omics, and clinical proteomics. 

The articles in this Special Issue shall demonstrate the potential of these techniques and technologies to answer important biological, biochemical, biomedical, and clinical questions and will demonstrate to the readers the valuable and continuing contribution of modern mass spectrometry to bioscience.

 

Dr. Rene Zahedi
Prof. Dr. Christoph Borchers
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mass Spectometry
  • Single-Cell 
  • Proteomics
  • Biosciences
  • Protein Imaging 
  • Omics

Published Papers (7 papers)

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Research

Jump to: Review

15 pages, 1950 KiB  
Article
A Dual-Acting Nitric Oxide Donor and Phosphodiesterase 5 Inhibitor Activates Autophagy in Primary Skin Fibroblasts
by Esther Martínez-Martínez, Paola Atzei, Christine Vionnet, Carole Roubaty, Stephanie Kaeser-Pebernard, Reto Naef and Jörn Dengjel
Int. J. Mol. Sci. 2022, 23(12), 6860; https://doi.org/10.3390/ijms23126860 - 20 Jun 2022
Cited by 2 | Viewed by 2323
Abstract
Wound healing pathologies are an increasing problem in ageing societies. Chronic, non-healing wounds, which cause high morbidity and severely reduce the quality of life of affected individuals, are frequently observed in aged individuals and people suffering from diseases affected by the Western lifestyle, [...] Read more.
Wound healing pathologies are an increasing problem in ageing societies. Chronic, non-healing wounds, which cause high morbidity and severely reduce the quality of life of affected individuals, are frequently observed in aged individuals and people suffering from diseases affected by the Western lifestyle, such as diabetes. Causal treatments that support proper wound healing are still scarce. Here, we performed expression proteomics to study the effects of the small molecule TOP-N53 on primary human skin fibroblasts and keratinocytes. TOP-N53 is a dual-acting nitric oxide donor and phosphodiesterase-5 inhibitor increasing cGMP levels to support proper wound healing. In contrast to keratinocytes, which did not exhibit global proteome alterations, TOP-N53 had profound effects on the proteome of skin fibroblasts. In fibroblasts, TOP-N53 activated the cytoprotective, lysosomal degradation pathway autophagy and induced the expression of the selective autophagy receptor p62/SQSTM1. Thus, activation of autophagy might in part be responsible for beneficial effects of TOP-N53. Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
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27 pages, 2425 KiB  
Article
Small Molecule Arranged Thermal Proximity Coaggregation (smarTPCA)—A Novel Approach to Characterize Protein–Protein Interactions in Living Cells by Similar Isothermal Dose–Responses
by Thomas Lenz and Kai Stühler
Int. J. Mol. Sci. 2022, 23(10), 5605; https://doi.org/10.3390/ijms23105605 - 17 May 2022
Cited by 4 | Viewed by 2910
Abstract
Chemical biology and the application of small molecules has proven to be a potent perturbation strategy, especially for the functional elucidation of proteins, their networks, and regulators. In recent years, the cellular thermal shift assay (CETSA) and its proteome-wide extension, thermal proteome profiling [...] Read more.
Chemical biology and the application of small molecules has proven to be a potent perturbation strategy, especially for the functional elucidation of proteins, their networks, and regulators. In recent years, the cellular thermal shift assay (CETSA) and its proteome-wide extension, thermal proteome profiling (TPP), have proven to be effective tools for identifying interactions of small molecules with their target proteins, as well as off-targets in living cells. Here, we asked the question whether isothermal dose–response (ITDR) CETSA can be exploited to characterize secondary effects downstream of the primary binding event, such as changes in post-translational modifications or protein–protein interactions (PPI). By applying ITDR-CETSA to MAPK14 kinase inhibitor treatment of living HL-60 cells, we found similar dose–responses for the direct inhibitor target and its known interaction partners MAPKAPK2 and MAPKAPK3. Extension of the dose–response similarity comparison to the proteome wide level using TPP with compound concentration range (TPP-CCR) revealed not only the known MAPK14 interaction partners MAPKAPK2 and MAPKAPK3, but also the potentially new intracellular interaction partner MYLK. We are confident that dose-dependent small molecule treatment in combination with ITDR-CETSA or TPP-CCR similarity assessment will not only allow discrimination between primary and secondary effects, but will also provide a novel method to study PPI in living cells without perturbation by protein modification, which we named “small molecule arranged thermal proximity coaggregation” (smarTPCA). Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
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15 pages, 2841 KiB  
Article
A Non-Hazardous Deparaffinization Protocol Enables Quantitative Proteomics of Core Needle Biopsy-Sized Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Specimens
by Georgia Mitsa, Qianyu Guo, Christophe Goncalves, Samuel E. J. Preston, Vincent Lacasse, Adriana Aguilar-Mahecha, Naciba Benlimame, Mark Basik, Alan Spatz, Gerald Batist, Wilson H. Miller, Jr., Sonia V. del Rincon, René P. Zahedi and Christoph H. Borchers
Int. J. Mol. Sci. 2022, 23(8), 4443; https://doi.org/10.3390/ijms23084443 - 18 Apr 2022
Cited by 6 | Viewed by 5793
Abstract
Most human tumor tissues that are obtained for pathology and diagnostic purposes are formalin-fixed and paraffin-embedded (FFPE). To perform quantitative proteomics of FFPE samples, paraffin has to be removed and formalin-induced crosslinks have to be reversed prior to proteolytic digestion. A central component [...] Read more.
Most human tumor tissues that are obtained for pathology and diagnostic purposes are formalin-fixed and paraffin-embedded (FFPE). To perform quantitative proteomics of FFPE samples, paraffin has to be removed and formalin-induced crosslinks have to be reversed prior to proteolytic digestion. A central component of almost all deparaffinization protocols is xylene, a toxic and highly flammable solvent that has been reported to negatively affect protein extraction and quantitative proteome analysis. Here, we present a ‘green’ xylene-free protocol for accelerated sample preparation of FFPE tissues based on paraffin-removal with hot water. Combined with tissue homogenization using disposable micropestles and a modified protein aggregation capture (PAC) digestion protocol, our workflow enables streamlined and reproducible quantitative proteomic profiling of FFPE tissue. Label-free quantitation of FFPE cores from human ductal breast carcinoma in situ (DCIS) xenografts with a volume of only 0.79 mm3 showed a high correlation between replicates (r2 = 0.992) with a median %CV of 16.9%. Importantly, this small volume is already compatible with tissue micro array (TMA) cores and core needle biopsies, while our results and its ease-of-use indicate that further downsizing is feasible. Finally, our FFPE workflow does not require costly equipment and can be established in every standard clinical laboratory. Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
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13 pages, 1622 KiB  
Article
Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis
by Michael X. Chen, Ho-Hsuan Su, Ching-Ya Shiao, Yu-Ting Chang, Ming-Chu Chang, Chih-Chin Kao, San-Yuan Wang, Hsi-Chang Shih and I-Lin Tsai
Int. J. Mol. Sci. 2021, 22(21), 11527; https://doi.org/10.3390/ijms222111527 - 26 Oct 2021
Cited by 2 | Viewed by 2036
Abstract
Type 1 autoimmune pancreatitis (AIP) is categorized as an IgG4-related disease (IgG4-RD), where a high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 [...] Read more.
Type 1 autoimmune pancreatitis (AIP) is categorized as an IgG4-related disease (IgG4-RD), where a high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 Fc-glycopeptides from populations in Asia were found to be isobaric ions when using LC-MS/MS as an analytical tool. In this study, an analytical workflow that coupled affinity purification and stable isotope dilution LC-MS/MS was developed to dissect IgG4 glycosylation profiles for autoimmune pancreatitis. Comparing the IgG4 and glycosylation profiles among healthy controls, patients with pancreatic ductal adenocarcinoma (PDAC), and AIP, the IgG4 glycosylations from the AIP group were found to have more digalactosylation (compared to PDAC) and less monogalactosylation (compared to HC). In addition, higher fucosylation and sialylation profiles were also discovered for the AIP group. The workflow is efficient and selective for IgG4 glycopeptides, and can be used for clinical biosignature discovery. Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
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19 pages, 2434 KiB  
Article
Mass Spectrometric and Bio-Computational Binding Strength Analysis of Multiply Charged RNAse S Gas-Phase Complexes Obtained by Electrospray Ionization from Varying In-Solution Equilibrium Conditions
by Cornelia Koy, Kwabena F. M. Opuni, Bright D. Danquah, Andrei Neamtu and Michael O. Glocker
Int. J. Mol. Sci. 2021, 22(19), 10183; https://doi.org/10.3390/ijms221910183 - 22 Sep 2021
Cited by 6 | Viewed by 1480
Abstract
We investigated the influence of a solvent’s composition on the stability of desorbed and multiply charged RNAse S ions by analyzing the non-covalent complex’s gas-phase dissociation processes. RNAse S was dissolved in electrospray ionization-compatible buffers with either increasing organic co-solvent content or different [...] Read more.
We investigated the influence of a solvent’s composition on the stability of desorbed and multiply charged RNAse S ions by analyzing the non-covalent complex’s gas-phase dissociation processes. RNAse S was dissolved in electrospray ionization-compatible buffers with either increasing organic co-solvent content or different pHs. The direct transition of all the ions and the evaporation of the solvent from all the in-solution components of RNAse S under the respective in-solution conditions by electrospray ionization was followed by a collision-induced dissociation of the surviving non-covalent RNAse S complex ions. Both types of changes of solvent conditions yielded in mass spectrometrically observable differences of the in-solution complexation equilibria. Through quantitative analysis of the dissociation products, i.e., from normalized ion abundances of RNAse S, S-protein, and S-peptide, the apparent kinetic and apparent thermodynamic gas-phase complex properties were deduced. From the experimental data, it is concluded that the stability of RNAse S in the gas phase is independent of its in-solution equilibrium but is sensitive to the complexes’ gas-phase charge states. Bio-computational in-silico studies showed that after desolvation and ionization by electrospray, the remaining binding forces kept the S-peptide and S-protein together in the gas phase predominantly by polar interactions, which indirectly stabilized the in-bulk solution predominating non-polar intermolecular interactions. As polar interactions are sensitive to in-solution protonation, bio-computational results provide an explanation of quantitative experimental data with single amino acid residue resolution. Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
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Review

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18 pages, 2369 KiB  
Review
Identification and Affinity Determination of Protein-Antibody and Protein-Aptamer Epitopes by Biosensor-Mass Spectrometry Combination
by Loredana-Mirela Lupu, Pascal Wiegand, Daria Holdschick, Delia Mihoc, Stefan Maeser, Stephan Rawer, Friedemann Völklein, Ebrahim Malek, Frederik Barka, Sascha Knauer, Christina Uth, Julia Hennermann, Wolfgang Kleinekofort, Andreas Hahn, Günes Barka and Michael Przybylski
Int. J. Mol. Sci. 2021, 22(23), 12832; https://doi.org/10.3390/ijms222312832 - 27 Nov 2021
Cited by 10 | Viewed by 3758
Abstract
Analytical methods for molecular characterization of diagnostic or therapeutic targets have recently gained high interest. This review summarizes the combination of mass spectrometry and surface plasmon resonance (SPR) biosensor analysis for identification and affinity determination of protein interactions with antibodies and DNA-aptamers. The [...] Read more.
Analytical methods for molecular characterization of diagnostic or therapeutic targets have recently gained high interest. This review summarizes the combination of mass spectrometry and surface plasmon resonance (SPR) biosensor analysis for identification and affinity determination of protein interactions with antibodies and DNA-aptamers. The binding constant (KD) of a protein–antibody complex is first determined by immobilizing an antibody or DNA-aptamer on an SPR chip. A proteolytic peptide mixture is then applied to the chip, and following removal of unbound material by washing, the epitope(s) peptide(s) are eluted and identified by MALDI-MS. The SPR-MS combination was applied to a wide range of affinity pairs. Distinct epitope peptides were identified for the cardiac biomarker myoglobin (MG) both from monoclonal and polyclonal antibodies, and binding constants determined for equine and human MG provided molecular assessment of cross immunoreactivities. Mass spectrometric epitope identifications were obtained for linear, as well as for assembled (“conformational”) antibody epitopes, e.g., for the polypeptide chemokine Interleukin-8. Immobilization using protein G substantially improved surface fixation and antibody stabilities for epitope identification and affinity determination. Moreover, epitopes were successfully determined for polyclonal antibodies from biological material, such as from patient antisera upon enzyme replacement therapy of lysosomal diseases. The SPR-MS combination was also successfully applied to identify linear and assembled epitopes for DNA–aptamer interaction complexes of the tumor diagnostic protein C-Met. In summary, the SPR-MS combination has been established as a powerful molecular tool for identification of protein interaction epitopes. Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
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14 pages, 766 KiB  
Review
Proteomics of Cryptococcus neoformans: From the Lab to the Clinic
by Ben Muselius, Shay-Lynn Durand and Jennifer Geddes-McAlister
Int. J. Mol. Sci. 2021, 22(22), 12390; https://doi.org/10.3390/ijms222212390 - 17 Nov 2021
Cited by 8 | Viewed by 3994
Abstract
Fungal pathogens cause an array of diseases by targeting both immunocompromised and immunocompetent hosts. Fungi overcome our current arsenal of antifungals through the emergence and evolution of resistance. In particular, the human fungal pathogen, Cryptococcus neoformans is found ubiquitously within the environment and [...] Read more.
Fungal pathogens cause an array of diseases by targeting both immunocompromised and immunocompetent hosts. Fungi overcome our current arsenal of antifungals through the emergence and evolution of resistance. In particular, the human fungal pathogen, Cryptococcus neoformans is found ubiquitously within the environment and causes severe disease in immunocompromised individuals around the globe with limited treatment options available. To uncover fundamental knowledge about this fungal pathogen, as well as investigate new detection and treatment strategies, mass spectrometry-based proteomics provides a plethora of tools and applications, as well as bioinformatics platforms. In this review, we highlight proteomics approaches within the laboratory to investigate changes in the cellular proteome, secretome, and extracellular vesicles. We also explore regulation by post-translational modifications and the impact of protein–protein interactions. Further, we present the development and comprehensive assessment of murine models of cryptococcal infection, which provide valuable tools to define the dynamic relationship between the host and pathogen during disease. Finally, we explore recent quantitative proteomics studies that begin to extrapolate the findings from the bench to the clinic for improved methods of fungal detection and monitoring. Such studies support a framework for personalized medical approaches to eradicate diseases caused by C. neoformans. Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
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