DNA-based nanomachines are self-assembled DNA superstructures that harness chemical free energy to perform mechanical work. The development of DNA machines has benefited greatly from the achievements in both structural and dynamic DNA nanotechnology. In this review, the configurations of DNA machines, fuel systems, and operations are discussed to outline the evolving paths of DNA machines. The focus is on the smart mechanical behavior of DNA machines, from the standpoint of upgrading the complexity of DNA nanostructures, cooperative activation of multimachinary systems, and the establishment of a network of the mechanical states. In the end, the challenges are highlighted and possible solutions are proposed to push forward smart DNA nanomachines, with the goal of creating biomimicking systems. Insights are also provided into the potential applications of the DNA machines with designable intelligence.
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