A DNA Molecular Robot Autonomously Walking on the Cell Membrane to Drive the Cell Motility

The synthetic molecular robot 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 a cell to migrate. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise locomote on the membrane-floating cell-surface receptors in a stochastic manner, 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. Together, we have developed a novel strategy to engineer a cell-driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution.