Rapid and precise quantification of lymphocyte iron content by single cell inductively coupled plasma mass spectrometry

Abstract

Metals facilitate catalysis during cellular metabolism, but heterogeneity of metal content at single-cell level within and between cell populations is poorly characterized. This is important because deficiencies of biometals, for example iron, are enormously prevalent worldwide. Here we quantify metal content of single-cells using inductively-coupled plasma mass spectrometry. To develop the method, we used rhodium and iridium-intercalated Jurkat cells, obtaining >0.96% r2 cross-analytical correlation with mass cytometry. We quantified iron and calcium mass/cell for murine T-lymphocytes with 3% and 8% 2-sigma intra-precision, respectively, when assessing thousands of cells/minute. T-lymphocytes exposed to a 625-fold difference in extracellular iron concentrations maintained close iron homeostatic control, varying [~]20% in iron content. Nevertheless, this relatively small variation strongly correlated with changes in cellular activation characteristics measured by flow cytometry. We also assessed human B-cell iron content, which was [~]10-fold higher than murine T-lymphocytes. Overall, we demonstrate rapid iron quantification at single-cell level in different cell types and relate cellular iron content to cell function. TeaserPrecise and rapid iron metallomics of lymphocytes by single cell ICP-MS is a powerful approach for accessing signatures of immunological status.