Rivera-Fuentes, PabloWrobel, Alexandra T.Zastrow, Melissa L.Khan, MustafaGeorgiou, JohnLuyben, Thomas T.Roder, John C.Okamoto, KenichiLippard, Stephen J.2019-10-302019-10-302019-10-30201510.1039/C4SC03388Dhttps://infoscience.epfl.ch/handle/20.500.14299/162487Imaging mobile zinc in acidic environments remains challenging because most small-mol. optical probes display pH-dependent fluorescence. Here we report a reaction-based sensor that detects mobile zinc unambiguously at low pH. The sensor responds reversibly and with a large dynamic range to exogenously applied Zn2+ in lysosomes of HeLa cells, endogenous Zn2+ in insulin granules of MIN6 cells, and zinc-rich mossy fiber boutons in hippocampal tissue from mice. This long-wavelength probe is compatible with the green-fluorescent protein, enabling multicolor imaging, and facilitates visualization of mossy fiber boutons at depths of \textgreater100 μm, as demonstrated by studies in live tissue employing two-photon microscopy.Acidic environmentacidic vesicle tissue zinc unambiguous detection fluorescence emitting probeFluorescenceGreen fluorescent proteinInsulin granulesLong wavelengthMulticolor imagingOptical probeProbesSmall moleculesTissueTwo photon microscopyZinctext::journal::journal article::research article