Illuminating Cellular Biochemistry: Fluorogenic Chemogenetic Biosensors for Biological Imaging

Cellular activity is defined by the precise spatiotemporal regulation of various components, such as ions, small molecules, or proteins. Studying cell physiology consequently requires the optical recording of these processes, notably by using fluorescent biosensors. The recent development of various fluorogenic systems greatly expanded the palette of reporters to be included in these sensors design. Fluorogenic reporters consist of a protein or RNA tag that can complex either an endogenous or a synthetic fluorogenic dye (so-called fluorogen). The intrinsic nature of these tags, along with the high tunability of their cognate chromophore provide interesting features such as far-red to near-infrared emission, oxygen independence, or unprecedented color versatility. These engineered photoreceptors, self-labelling proteins, or noncovalent aptamers and protein tags were rapidly identified as promising reporters to observe biological events. This Minireview focuses on the new perspectives they offer to design unique and innovative biosensors, thus pushing the boundaries of cellular imaging.