Since the discovery of an extracellular Ca2+-sensing receptor (CaSR, Fig. 1, right) in 1993, an increasing number of studies have demonstrated its functions in various organs, thereby revealing that extracellular Ca2+ acts as a first messenger. However, currently, there is little tool for imaging Ca2+ dynamics in extracellular regions. Inspired by the fact that clusters of carboxylic acids in CaSR serve as Ca2+-binding sites, we have developed conceptually new fluorescent Ca2+ sensors based on polyacrylic acid (PAA) and its gel. PAA is known to undergo single-chain aggregation in the presence of Ca2+. We have shown that when aggregation-induced emission luminogen (e.g., tetraphenylethene: TPE) is attached to the side chain of PAA (PAA-TPEx and g-PAA-TPEx, Fig. 1, left), the conformational state of the PAA-chain at a given Ca2+ concentration ([Ca2+]) can be translated into the fluorescence intensity (Fig. 2). Importantly, chemically cross-linked gel (g-PAA-TPEx) exhibits a similar Ca2+ responsiveness, providing a solid-state Ca2+-sensor. The PAA-TPEx and g-PAA-TPEx not only have a millimolar (mM)-order apparent dissociation constant (Kd), compatible with extracellular [Ca2+], but also exhibit sufficient dynamic range and selectivity in the presence of physiological concentrations of biologically relevant ions and molecules. By virtue of these properties, g-PAA-TPEx allowed the monitoring of submillimolar fluctuations of Ca2+ in flowing analytes that contain mM [Ca2+]. In this presentation, we will describe the Ca2+-sensing properties of PAA-TPEx and g-PAA-TPEx in relation to its potential application for a biosensor.

Bioinspired design of synthetic polymer-based Ca2+ sensor for the realization of extracellular Ca2+ imaging

254th National Meeting (2017)

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