Biomimetic Sensing System for Tracing Pb²⁺ Distribution in Living Cells Based on the Metal-Peptide Supramolecular...

Metal-peptide interactions provide plentiful resource and design principles for developing functional biomaterials and smart sensors. Pb²⁺, as a borderline metal ion, has versatile coordination modes. The interference from competing metal ions and endogenous chelating species greatly challenges Pb²⁺ analysis, especially in complicated living biosystems. Herein, a biomimetic peptide-based fluorescent sensor GSSH-2TPE was developed, starting from the structure of a naturally occurring peptide glutathione. Lewis acid-base theory was employed to guide the molecular design and tune the affinity and selectivity of the targeting performance. The integration of peptide recognition and aggregation-induced emission effect provides desirable sensing features, including specific turn-on response to Pb²⁺ over 18 different metal ions, rapid binding, and signal output, as well as high sensitivity with a detection limit of 1.5 nM. Mechanism investigation demonstrated the balance between the chelating groups, and the molecular configuration of the sensor contributes to the high selectivity toward Pb²⁺ complexation. The ion-induced supramolecular assembly lights up the bright fluorescence. The ability to image Pb²⁺ in living cells was exhibited with minimal interference from endogenous biothiols, no background fluorescence, and good biocompatibility. With good cell permeability, GSSH-2TPE can monitor changes in Pb²⁺ levels and biodistribution and thus predict possible damage pathways. Such metal-peptide interaction-based sensing systems offer tailorable platforms for designing bioanalytical tools and show great potential for studying the cell biology of metal ions in living biosystems.