Dynamic mapping of spontaneously produced H2S in the entire cell space and in live animals using a rationally designed molecular switch

Abstract

Hydrogen sulfide (H₂S) is a key signaling molecule in the cytoprotection, vascular mediation and neurotransmission of living organisms. In-depth understanding of its production, trafficking, and transformation in cells is very important in the way H₂S mediates cellular signal transductions and organism functions; it also motivates the development of H₂S probes and imaging technologies. A fundamental challenge, however, is how to engineer probes with sensitivity and cellular penetrability that allow detection of spontaneous production of H₂S in the entire cell space and live animals. Here, we report a rationally designed molecular switch capable of accessing all intracellular compartments, including the nucleus, lysosomes and mitochondria, for H₂S detection. Our probe comprised three functional domains (H₂S sensing, fluorescence, and biomembrane penetration), could enter almost all cell types readily, and exhibit a rapid and ultrasensitive response to H₂S (≤120-fold fluorescence enhancement) for the dynamic mapping of spontaneously produced H₂S as well as its distribution in the whole cell. In particular, the probe traversed blood/tissue/cell barriers to achieve mapping of endogenous H₂S in metabolic organs of a live Danio rerio (zebrafish). These results open-up exciting opportunities to investigate H₂S physiology and H₂S-related diseases.