Bioinspired peptide sensors with tailorable structure for specific and in-situ tracking of Hg2+ biodistribution in living cells upon acute exposure

Abstract

Metal-biomolecule interactions that are ubiquitous in nature provide fundamental knowledge and rich structural motifs for the development of functional molecules and smart sensors. In this work, inspired by the active sites in metalloproteins, a biomimetic peptide sensor was designed for the selective recognition and activatable sensing of Hg²⁺ in living biosystems. Tetraphenylethylene (TPE) with typical aggregation-induced emission (AIE) behavior, was introduced as the activatable signal transducer to enable high signal-to-background signaling. The tailorable side chains and flexible peptide linkage were exploited to tune the coordination affinity, selectivity, and fluorescence response toward Hg²⁺. Benefiting from the rapid response (1 min), high specificity and nanomolar sensitivity, the peptide sensor allows investigating the mechanism of acute toxicity of Hg²⁺. Capable of penetrating plasma membrane, the peptide sensor revealed the dosage-dependent and dynamic subcellular biodistribution behavior of Hg²⁺. The finding that Hg²⁺ preferentially accumulates and rapidly enriches in nucleoli of cells upon short exposure, evidences the adverse effect toward ribosome biogenesis and the resultant genetic deficiencies. These results highlight the peptide sensors as promising tools for not only on-site detection, but also studying the cell biology and toxicology of this metal ion in living biosystems.

Keywords: Aggregation-induced emission; Biomimetic receptor; Hg(2+); Peptide sensor; Subcellular tracking.