适体
化学
受体
内吞作用
配体(生物化学)
细胞
细胞膜
DNA
循环肿瘤细胞
单纯形
癌细胞
细胞生物学
膜
细胞粘附
细胞表面受体
生物物理学
计算生物学
分子生物学
生物化学
癌症
生物
遗传学
转移
数学
几何学
作者
Min Li,Hong‐ming Ding,Meihua Lin,Fangfei Yin,Lu Song,Xiuhai Mao,Li Fan,Zhilei Ge,Lihua Wang,Xiaolei Zuo,Yu‐qiang Ma,Chunhai Fan
摘要
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.
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