High-Affinity Labeling and Tracking of Individual Histidine-Tagged Proteins in Live Cells Using Ni²⁺ Tris-nitrilotriacetic Acid Quantum Dot Conjugates

Investigation of many cellular processes using fluorescent quantum dots (QDs) is hindered by the nontrivial requirements for QD surface functionalization and targeting. To address these challenges, we designed, characterized and applied QD−trisNTA, which integrates tris-nitrilotriacetic acid, a small and high-affinity recognition unit for the ubiquitous polyhistidine protein tag. Using QD−trisNTA, we demonstrate two-color QD tracking of the type-1 interferon receptor subunits in live cells, potentially enabling direct visualization of protein−protein interactions at the single molecule level.