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Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self‐propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane‐floating cell‐surface receptors in a stochastic manner and simultaneously trigger the receptor‐dimerization to activate downstream signaling for cell motility. The cell membrane‐associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell‐driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution. [ABSTRACT FROM AUTHOR]

Selective modulation of ligand–receptor interaction is essential in targeted therapy. In this study, we design an intelligent "scan and unlock" DNA automaton (SUDA) system to equip a native protein‐ligand with cell‐identity recognition and receptor‐mediated signaling in a cell‐type‐specific manner. Using embedded DNA‐based chemical reaction networks (CRNs) on the cell surface, SUDA scans and evaluates molecular profiles of cell‐surface proteins via Boolean logic circuits. Therefore, it achieves cell‐specific signal modulation by quickly unlocking the protein‐ligand in proximity to the target cell‐surface to activate its cognate receptor. As a proof of concept, we non‐genetically engineered hepatic growth factor (HGF) with distinct logic SUDAs to elicit target cell‐specific HGF signaling and wound healing behaviors in multiple heterogeneous cell types. Furthermore, the versatility of the SUDA strategy was shown by engineering tumor necrotic factor‐α (TNFα) to induce programmed cell death of target cell subpopulations through cell‐specific modulation of TNFR1 signaling. [ABSTRACT FROM AUTHOR]

Cell manipulation, DNA robots, DNA walkers, DNAzymes, membrane receptors Innenrücktitelbild: A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility (Angew. Keywords: cell manipulation; DNA robots; DNA walkers; DNAzymes; membrane receptors EN cell manipulation DNA robots DNA walkers DNAzymes membrane receptors 26615 26615 1 12/01/21 20211206 NES 211206 B Ein molekularer DNA-Roboter b wurde entwickelt, der sich autonom auf der Zellmembran bewegt, um die Zellmotilität zu steuern. [Extracted from the article]

Keywords: cell manipulation; DNA robots; DNA walkers; DNAzymes; membrane receptors EN cell manipulation DNA robots DNA walkers DNAzymes membrane receptors 26411 26411 1 12/01/21 20211206 NES 211206 B A DNA molecular robot b autonomously walking on a cell membrane to drive cell motility has been developed. Cell manipulation, DNA robots, DNA walkers, DNAzymes, membrane receptors Inside Back Cover: A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility (Angew. [Extracted from the article]