Dynamic Supramolecular Interaction in Cucurbit[7]uril Host-Guest Complex Enables Autonomous Single Molecule Blinking and Super-Resolution Imaging in Cells and Tissues

Synthetic supramolecular host-guest complexes are inherently dynamic as they employ weak and reversible noncovalent interactions for their recognition process. This dynamic behavior allows host-guest chemistry to be employed for various state of the art applications. Herein, we demonstrate the use of the dynamic supramolecular interaction to enable nanoscopic imaging inside cells and tissues. This imaging method exploits repetitive and transient binding of fluorescently labeled hexamethylenediamine (HMD) guest molecule to complementary cucurbit[7]uril (CB[7]) host to obtain stochastic switching between fluorescence ON- and OFF-states. Through connecting CB[7] hosts to targeting ligands (e.g., antibodies and small molecules), we show that this autonomous blinking enables two-dimensional (2D) and 3D super-resolution imaging of proteins in fixed cells and tissues. Finally, we exploited the capability of host-guest molecules to maintain their interaction specificity in the complexity of the live intracellular environment to obtain super-resolution actin imaging in living HeLa cell.