A Water-soluble, Cell-permeable Mn(II) Sensor Enables Visualization of Manganese Dynamics in Live Mammalian Cells

Central roles of Mn2+ ions in immunity, brain function, and photosynthesis, necessitate probes for tracking this essential metal in living systems. However, developing a cell-permeable, fluorescent sensor for selective imaging of Mn2+ ions in the aqueous cellular milieu has remained a challenge. This is because Mn2+ is a weak binder to ligand scaffolds when compared to other physiological metal ions, in water. Here we report a water-soluble, fluorescent turn-on, Mn2+ selective sensor that enters living cells within 15 min of direct incubation and enables imaging of Mn2+ dynamics in live mammalian cells. We reveal differential Mn2+ localization and dynamics in disease model cells replicating conditions of Mn-induced Parkinsonism compared to normal cells. The computationally-designed sensor with a 620 nM limit-of-detection for Mn2+ in water, distinctly overcomes selectivity, sensitivity, and cell-impermeability issues associated with the few reported Mn2+ probes, thus opening floodgates to elucidate the hitherto intractable mammalian Mn2+ homeostasis.