Novel Secondary Ion Mass Spectrometry Methods for the Examination of Metabolic Effects at the Cellular and Subcellular Levels

Abstract

The behavior of an animal has substantial effects on its metabolism. Such effects, including changes in the lipid composition of different organs, or changes in the turnover of the proteins, have typically been observed using liquid mass spectrometry methods, averaging the effect of animal behavior across tissue samples containing multiple cells. These methods have provided the scientific community with valuable information, but have limited resolution, making it difficult if not impossible to examine metabolic effects at the cellular and subcellular levels. Recent advances in the field of secondary ion mass spectrometry (SIMS) have made it possible to examine the metabolic effects of animal behavior with high resolution at the nanoscale, enabling the analysis of the metabolic effects of behavior on individual cells. In this review we summarize and present these emerging methods, beginning with an overview of the SIMS technique. We then discuss the specific application of nanoscale SIMS (NanoSIMS) to examine cell behavior. This often requires the use of isotope labeling to highlight specific sections of the cell for analysis, an approach that is presented at length in this review article. We also present SIMS applications concerning animal and cell behavior, from development and aging to changes in the cellular activity programs. We conclude that the emerging group of SIMS technologies represents an exciting set of tools for the study of animal behavior and of its effects on internal metabolism at the smallest possible scales.

A web-based histology atlas for the freshwater sentinel speciesDaphnia magna

“…This atlas is envisioned to serve as a potential integrative platform for other omics data and to facilitate the addition of context from other imaging modalities. Notably, adding microanatomical context to molecular analyses including transcriptomics (Marx, 2021), secondary ion mass spectrometry (Bonnin and Rizzoli, 2020), and desorption electrospray ionization-mass spectrometry (Smith et al, 2022), has become a new priority, and typically relies on tissue histology to which the data can be mapped. While 3D imaging modalities such as fluorescence-based confocal or laser sheet microscopy (Connelly et al, 2015; Mittmann et al, 2014), or X-ray histotomography (Ding et al, 2019; Yakovlev et al, 2022) provide the 3-dimensionality of anatomical structures that is lacking in histology, differential staining using a range of histochemical stains provides the basic understanding of tissue and cell types that can eventually be linked to the grayscale morphologies characteristic of most 3D imaging modalities.…”

“…DaHRA is envisioned to serve as a potential integrative platform for -omics data and to facilitate the addition of context from other imaging modalities. Molecular analyses including spatial transcriptomics (62), secondary ion mass spectrometry (63), and desorption electrospray ionization-mass spectrometry (64) typically rely on tissue histology to which the data can be mapped, and adding microanatomical context to molecular analyses has become a new priority. DaHRA can be used as a framework facilitating the addition of the -omics data.…”

How Do We Explore Heterogeneity in Turnover of Musculoskeletal Proteins?

“…Advances within secondary ion mass spectrometry (SIMS), as either time-of-flight SIMS or NanoSIMS, will also be of great interest in the future to study tissue heterogeneity. 9 With this approach, in situ detection of tracer labeling from tissue sections will elucidate possible region-specific differences in protein turnover. Therefore, DPP and SIMS are important approaches to be considered for the future toolbox of methods to determine protein turnover rates of musculoskeletal tissues, to be able to distinguish between dynamic and inactive protein pools, or between pools with a slow or fast protein turnover rates.…”

Visualizing Surface Phase Separation in PS PMMA Polymer Blends at the Nanoscale

“…7 Spectromicroscopic techniques like Fourier-transform infrared 13 and confocal Raman microscopies 14 provide a plethora of chemical information with molecular specificity, however their spatial resolution remains diffraction-limited to the sub-micron scale. Amongst the nanoscale techniques, nanoscale secondary ion mass spectrometry is destructive and requires isotopic labelling, 15 whilst sampling depth of photothermally-induced resonance (commonly known as AFM-IR) is a few micrometers, thus having low vertical resolution and sensitivity. 16 Transmission electron microscopy (TEM) can be used to study phase separation in polymers.…”