Bioinspired design of a polymer gel sensor for the realization of extracellular Ca(2+) 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.