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Cell-Membrane-Anchored Synthetic Dynamic DNA Circuits for Signaling Transient Cell Migration

Nina Lin,O. Yu,Yunlong Qin,Songqin Liu,I. Willner,Yuanjian Zhang,Zhixin Zhou

Published 2025 in Journal of the American Chemical Society

ABSTRACT

A DNA reaction circuit consisting of components E/Q1, E1/T1, F/Q1, and F1/T1 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.

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