Magnesium is the most abundant divalent cation in mammalian cells, with a number of very important roles in cellular function. Fluorescent imaging has emerged as the most effective tool to study intracellular Mg2+, but current available sensors lack the combination of selectivity and spatial resolution required to help elucidate the many unanswered questions about magnesium homeostasis, and its interplay with various signaling molecules in cells. Sensors based on b-dicarbonyl binding motifs offer superior metal selectivity profiles over those of commercially available o-aminophenol-N,N,O-triacetic acid (APTRA) based chelators. However, we demonstrated that complex binding schemes leading to formation of ternary complexes may cause these low-denticity indicators to co-report on various intracellular species, challenging the interpretation of imaging experiments and highlighting the need for a deeper understanding of the factors that influence probe selectivity. Here we describe new approaches aimed at achieving true speciation information regarding cellular magnesium, and strategies for targeting small-molecule indicators for the study of ion compartmentalization in intracellular organelles.

Lighting-up metals: Fluorescent tools for the study of magnesium homeostasis

248th National Meeting (2014)

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