Cell-Membrane-Anchored Synthetic Dynamic DNA Circuits for Signaling Transient Cell Migration
Nina Lin, Yu Ouyang, Yunlong Qin, Songqin Liu, Itamar Willner, Yuanjian Zhang, Zhixin Zhou
Abstract
in which each includes the antimesenchymal epithelial transition (Met) receptor aptamer sequence is anchored within MCF-7 cells to emulate the natural signaling network on the live cell membrane. Subjecting the membrane-integrated circuit to an auxiliary fuel strand, in the presence of a nicking enzyme, results in the dynamic reconfiguration of the circuit into a constitutional dynamic network, CDN, in which the pre-engineered duplex interactions between the constituents lead to allosterically stabilized Met-dimer complexes. The concomitant nickase-induced separation of the CDN leads to the parent reaction circuit, and to the transient formation and depletion of the Met-dimer complex. By labeling the components comprising the reaction circuits with fluorophores, the dynamic transient reconfiguration of the CDN and the accompanying Met-dimer formation and separation within the cell membranes are characterized by temporal confocal fluorescence microscopy imaging. Moreover, the transient formation of the Met-dimer in the MCF-7 cell membrane induces intracellular signaling and activation of the Akt/FAK phosphorylation pathway. This is reflected by the network-guided control over the transient migration/motility functions of the MCF-7 cells.