DNA Framework-Programmed Cell Capture via Topology-Engineered Receptor-Ligand Interactions.
Min LiHong-Ming DingMeihua LinFangfei YinLu SongXiuhai MaoFan LiZhilei GeLihua WangXiaolei ZuoYuqiang MaChun-Hai FanPublished in: Journal of the American Chemical Society (2019)
Receptor-ligand interactions (RLIs) that play pivotal roles in living organisms are often depicted with the classic keys-and-locks model. Nevertheless, RLIs on the cell surface are generally highly complex and nonlinear, partially due to the noncontinuous and dynamic distribution of receptors on extracellular membranes. Here, we develop a tetrahedral DNA framework (TDF)-programmed approach to topologically engineer RLIs on the cell membrane, which enables active recruitment-binding of clustered receptors for high-affinity capture of circulating tumor cells (CTCs). The four vertices of a TDF afford orthogonal anchoring of ligands with spatial organization, based on which we synthesized n-simplexes harboring 1-3 aptamers targeting epithelial cell adhesion molecule (EpCAM) that are overexpressed on the membrane of tumor cells. The 2-simplex with three aptamers not only shows increased binding affinity (∼19-fold) but prevents endocytosis by cells. By using 2-simplex as the capture probe, we demonstrate the high-efficiency CTC capture, which is challenged in real clinical breast cancer patient samples. This TDF-programmed platform thus provides a powerful means for studying RLIs in physiological settings and for cancer diagnosis.
Keyphrases
- circulating tumor cells
- circulating tumor
- cell adhesion
- high efficiency
- cell surface
- nucleic acid
- binding protein
- induced apoptosis
- papillary thyroid
- single molecule
- single cell
- cell cycle arrest
- cell therapy
- squamous cell carcinoma
- high throughput
- dna binding
- cancer therapy
- mass spectrometry
- mouse model
- living cells
- young adults
- signaling pathway
- childhood cancer
- transcription factor
- stem cells