Classifying Cell Types with DNA-Encoded Ligand-Receptor Interactions on the Cell Membrane.

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.