Metabolites can regulate protein activity, gene expression and the availability of cellular energy and building blocks, thus acting as key modulators of biological functions. Metabolites are synthetized via biosynthetic pathways that are organized in functional tissues and subcellular structures that enable the trafficking of substrates, intermediates, and products. Charting this heterogenous organization of metabolism at cellular and sub-cellular resolution is therefore crucial to understanding biological functions from a systems-level standpoint.<br/>Single cell (SC) mass spectrometry (MS) based metabolomics is a promising approach for exploring the metabolic diversity of tissues and cells. Yet, this technique calls for improved metabolome coverage, resolution, and sensitive measurements. Here we discuss the utility of nanostructure imaging mass spectrometry (NIMS) metabolomics with perfluorinated gold nanoparticles (f-AuNPs) for charting metabolism heterogeneity in space, from whole organisms to tissues and single cells. We showcase the application of this technology for the global analysis of functional rearrangements in the metabolic organization of mice under different diet regimens (standard, fiber depleted, fiber and polysaccharide depleted). NIMS with f-AuNPs permits heterogeneous molecular coverage, allowing the direct detection of carbohydrates, lipids, bile acids, sulfur metabolites, amino acids, nucleotides as well as other small molecules of biological relevance with exquisite sensitivity, high-resolution and minimal metabolite dislocation in space. Finally, we provide a perspective on future applications of NIMS for SC-MS metabolomics at cellular and subcellular level.

Investigating metabolism heterogeneity by nanostructure imaging mass spectrometry: From whole organisms to single cells

ACS Spring 2022

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