Modulating loop flexibility reversibly switches DNA nanocage assembly

Developing a general control strategy applicable to distinct types of stimuli would be highly valuable in dynamic DNA nanotechnology. Herein, we present a versatile strategy for reversible DNA self-assembly based on modulating the flexibility of an independent, dedicated control loop. Using a cytosine-rich loop sequence as a model, we demonstrated that bidirectional tuning of loop flexibility sufficed to govern reversible DNA tetrahedron assembly: one tuning strategy involved pH-triggered interconversion between the i-motif and a random coil with greater flexibility; the other employed toehold-mediated strand displacement reactions to switch between the i-motif and a DNA duplex with lower flexibility. This strategy offers a versatile and programmable platform for the construction of dynamic DNA systems, with broad implications in molecular machines, biosensing, and drug delivery.