Tumor Cell-Specific Signal Processing Platform Controlled by ATP for Non-invasive Modulation of Cellular Behavior
Guofang Zhang, Shuzhen Yue, Hongyan Geng, Xinyan Wang, Tian Tian, Zhumei Cui, Sai Bi
Abstract
Regulating the spatial distribution of membrane receptors can artificially reprogram cellular behaviors, which play a critical biological role in various physiological and pathological processes. Herein, we construct a tumor cell-specific signal processing platform (TCS-SPP) for controlled promotion/inhibition of cellular-mesenchymal epithelial transition factor (c-Met) receptor dimerization to noninvasively modulate cellular behaviors. Upon the dual-aptamer recognition in the upstream input signal circuit (UISC) to discriminate target cancer cells, the membrane-anchored DNA signal processor (DSP) is activated for signal amplification via rolling circle amplification (RCA) followed by the working of an ATP molecular switch for signal conversion, achieving receptor modulation in the downstream output signal circuit (DOSC). Benefiting from the rigid structure of DSP, the protective effect, and spatial confinement effect of RCA products, this TCS-SPP has demonstrated good performance in accurately modulating cellular behavior such as cell migration, invasion, and proliferation, showing great potential for targeted cancer therapy and biomedical engineering applications.