Classifying Cell Types with DNA-Encoded Ligand–Receptor Interactions on the Cell Membrane
Luhao Zhang, Fei Wang, Qian Li, Lihua Wang, Chunhai Fan, Jiang Li, Ying Zhu
Abstract
Clustering, endocytosis, and intracellular transport of molecules on the cell membrane are critically dependent on the type of cells. However, the membrane-associated redistribution of molecules has not been exploited to realize cell classification for diagnostic purposes. Here, we develop a set of DNA-encoded artificial receptors and ligands to monitor the cell membrane redistribution. In this system, a cholesterol-modified single-stranded DNA strand serves as the receptor localized on the membrane, and a tetrahedral DNA framework (TDF) nanostructure with a complementary overhang serves as the ligand. The DNA-encoded receptor-ligand interaction is highly orthogonal, mimicking the dynamics of natural receptors and ligands on cells. We demonstrate that the dynamics of membrane redistribution can be resolved by the dual-color fluorescent patterns of the receptor-ligand interactions in a single image, which can be exploited to classify cell lines with high fidelity. This DNA-encoded method thus holds great promise for cell typing and diagnosis.