The intrinsic complexity of many mesoscale (10-100 nm) cellular machineries makes it challenging to elucidate their topological arrangement and transition dynamics. Here, we exploit DNA origami nanospring as a model system to demonstrate that tens of piconewton linear force can modulate higher-order conformation dynamics of mesoscale molecular assemblies. By switching between two chemical structures (i.e., duplex and tetraplex DNA) in the junctions of adjacent origami modules, the corresponding stretching or compressing chemo-mechanical stress reversibly flips the backbone orientations of the DNA nanosprings. Both coarse-grained molecular dynamics simulations and atomic force microscopy measurements reveal that such a backbone conformational switch does not alter the right-handed chirality of the nanospring helix. This result suggests that mesoscale helical handedness may be governed by the torque, rather than the achiral orientation, of nanospring backbones. It offers a topology-based caging/uncaging concept to present chemicals in response to environmental cues in solution.
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