Ligand bound quantum dots for intracellular imaging of neural receptors

Quantum dots (QDs) may serve as improved platforms for the complex modulation and ultra-sensitive imaging of molecular signaling in cells. The time course and spatial localization of activated ligand-receptor complexes and their trafficking within cells is becoming increasingly understood as vital for propagating cell signals. However, the movement and fate of ligand-receptor pairs inside cells is difficult to define with current technologies. We have studied the intracellular trafficking of TrkA receptors using QDs conjugated with nerve growth factor, a neuropeptide ligand critical for nervous system development and regulation. We find that NGF-QDs bind and activate TrkA surface receptors in PC12 neurons. Spatiotemporal maps of TrkA-NGF-QD endocytosis and translocation can be directly visualized with single QD resolution. Moreover, single molecule tracking experiments indicates that QDs complexes are actively shuttled over long distances within newly-sprouted neuronal processes. These results indicate that QDs can serve as effective high-resolution probe to track ligand-receptor function in the interior of cells.