Insight to Functional Conformation and Noncovalent Interactions of Protein-Protein Assembly Using MALDI Mass Spectrometry

Noncovalent interactions are the keys to the structural organization of biomolecule e.g., proteins, glycans, lipids in the process of molecular recognition processes e.g., enzyme-substrate, antigen-antibody. Protein interactions lead to conformational changes, which dictate the functionality of that protein-protein complex. Besides biophysics techniques, noncovalent interaction and conformational dynamics, can be studied via mass spectrometry (MS), which represents a powerful tool, due to its low sample consumption, high sensitivity, and label-free sample. In this review, the focus will be placed on Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) and its role in the analysis of protein-protein noncovalent assemblies exploring the relationship within noncovalent interaction, conformation, and biological function.publishedVersion© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Polymerization as a strategy to improve small organic matrices for low-molecular-weight compound analytics with MALDI MS and MALDI MS imaging

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by American Chemical Society in ACS Applied Polymer Materials on 07/07/2021.Available online: https://pubs.acs.org/doi/10.1021/acsapm.1c00665acceptedVersio

Visualization of Small Intact Proteins in Breast Cancer FFPE Tissue

acceptedVersio

Maleic anhydride proton sponge: from the development to the application in MALDI-MSI of tumor metabolism in glioblastoma

Giampà M. Maleic anhydride proton sponge: from the development to the application in MALDI-MSI of tumor metabolism in glioblastoma. Bielefeld; 2017

Insight to Functional Conformation and Noncovalent Interactions of Protein-Protein Assembly Using MALDI Mass Spectrometry

Noncovalent interactions are the keys to the structural organization of biomolecule e.g., proteins, glycans, lipids in the process of molecular recognition processes e.g., enzyme-substrate, antigen-antibody. Protein interactions lead to conformational changes, which dictate the functionality of that protein-protein complex. Besides biophysics techniques, noncovalent interaction and conformational dynamics, can be studied via mass spectrometry (MS), which represents a powerful tool, due to its low sample consumption, high sensitivity, and label-free sample. In this review, the focus will be placed on Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) and its role in the analysis of protein-protein noncovalent assemblies exploring the relationship within noncovalent interaction, conformation, and biological function.</jats:p

Unravel the Local Complexity of Biological Environments by MALDI Mass Spectrometry Imaging

Classic metabolomic methods have proven to be very useful to study functional biology and variation in the chemical composition of different tissues. However, they do not provide any information in terms of spatial localization within fine structures. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) does and reaches at best a spatial resolution of 0.25 μm depending on the laser setup, making it a very powerful tool to analyze the local complexity of biological samples at the cellular level. Here, we intend to give an overview of the diversity of the molecules and localizations analyzed using this method as well as to update on the latest adaptations made to circumvent the complexity of samples. MALDI MSI has been widely used in medical sciences and is now developing in research areas as diverse as entomology, microbiology, plant biology, and plant–microbe interactions, the rhizobia symbiosis being the most exhaustively described so far. Those are the fields of interest on which we will focus to demonstrate MALDI MSI strengths in characterizing the spatial distributions of metabolites, lipids, and peptides in relation to biological questions.</jats:p

Unravel the Local Complexity of Biological Environments by MALDI Mass Spectrometry Imaging

Classic metabolomic methods have proven to be very useful to study functional biology and variation in the chemical composition of different tissues. However, they do not provide any information in terms of spatial localization within fine structures. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) does and reaches at best a spatial resolution of 0.25 μm depending on the laser setup, making it a very powerful tool to analyze the local complexity of biological samples at the cellular level. Here, we intend to give an overview of the diversity of the molecules and localizations analyzed using this method as well as to update on the latest adaptations made to circumvent the complexity of samples. MALDI MSI has been widely used in medical sciences and is now developing in research areas as diverse as entomology, microbiology, plant biology, and plant–microbe interactions, the rhizobia symbiosis being the most exhaustively described so far. Those are the fields of interest on which we will focus to demonstrate MALDI MSI strengths in characterizing the spatial distributions of metabolites, lipids, and peptides in relation to biological questions

Multimodal methods to study protein aggregation and fibrillation

This chapter presents a selection of multimodal (combined) methods for the integral investigation of different proteins/peptides and their aggregation or fibrillation process in three levels of complexity. The first level considers the in vitro scenario where isolated polypeptides are investigated by low-resolution and atomistic techniques. The second and third levels consider protein aggregation in the cellular context in vitro (Level 2) and biological environments ex vivo and in vivo like tissue and biofluids (Level 3) to investigate the process of aggregation as close as possible to the pathological conditions. The selected examples are presented considering different protein/peptide structural transitions toward forming both nonfibrillar or fibrillar aggregates and the combinations of techniques that provide meaningful insights into the aggregation process in three levels of complexity.Fil: Herrera, Maria Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; ArgentinaFil: Giampà, Marco. Norwegian University of Science and Technology; NoruegaFil: Tonali, Nicolo. Universite Paris-Saclay. Faculté de Pharmacie; FranciaFil: Dodero, Veronica Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universitat Bielefeld; Alemani

Polymerization as a Strategy to Improve Small Organic Matrices for Low-Molecular-Weight Compound Analytics with MALDI MS and MALDI MS Imaging

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) and the corresponding visualizing technique MALDI MS imaging (MSI) are potent and widely used analytical methods in medical and pathological research. In recent years, the investigation of low-molecular-weight compounds (LMWCs) such as metabolites has moved increasingly into the focus. MALDI techniques require a matrix system, and small organic matrices (SOMs) are commonly used. While SOMs offer multiple advantages, such as broad analyte scopes and high ionization efficiencies, they also suffer from drawbacks, e.g., strong background interferences in the low-mass area (m/z < 1000) and low vacuum stability, which is particularly detrimental for LMWC analytics with high vacuum (HV) MALDI MS and MSI. Here, we apply polymerization as a strategy to alleviate these drawbacks while retaining the multiple advantages of SOMs. Vinyl groups were introduced to two SOMs, the state-of-the-art positive mode matrix 2,5-dihydroxybenzoic acid (DHB) as well as one of the few known dual polarity mode matrices, 7-methoxy-1-methyl-9H-pyrido[3,4-b]indole (harmine), and radical polymerization was performed to obtain polyethylene-based P(SOMs) carrying the corresponding SOMs as side chains. Compared to the corresponding SOMs, the synthesized P(SOMs) maintain optical properties in the solid state and have competitive performances regarding analyte scopes, ionization efficiencies, and dual polarity mode suitability. Additionally, both P(SOMs) are HV stable (μ10-7 mbar) and reveal no background interferences in the low-mass area (MALDI-silent). To assess a potential application in a clinical workflow, the P(SOMs) were applied on breast cancer xenografts and MALDI MSI measurements were carried out, demonstrating their ability to produce and spatially resolve positive and negative tissue-related ions directly from the cancer tissue. Polymerization is shown to be a promising strategy to make state-of-the-art SOMs MALDI silent and vacuum stable and yield easily handled matrices for clinical workflows