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

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.