Bioinspired design of a polymer gel sensor for the realization of extracellular Ca2+ imaging

Although the role of extracellular Ca 2+ draws increasing attention as a messenger in intercellular communications, there is currently no tool available for imaging Ca 2+ dynamics in extracellular regions. Here we report the first solid-state fluorescent Ca 2+ sensor that fulfills the essential requirements for realizing extracellular Ca 2+ imaging. Inspired by natural extracellular Ca 2+ -sensing receptors, we designed a particular type of chemically-crosslinked polyacrylic acid gel, which can undergo single-chain aggregation in the presence of Ca 2+ . By attaching aggregation-induced emission luminogen to the polyacrylic acid as a pendant, the conformational state of the main chain at a given Ca 2+ concentration is successfully translated into fluorescence property. The Ca 2+ sensor has a millimolar-order apparent dissociation constant compatible with extracellular Ca 2+ concentrations, and exhibits sufficient dynamic range and excellent selectivity in the presence of physiological concentrations of biologically relevant ions, thus enabling monitoring of submillimolar fluctuations of Ca 2+ in flowing analytes containing millimolar Ca 2+ concentrations.