Dynamic Control of DNA Origami Self-Assembly by Transcriptional Modules

Biological cells achieve adaptive and responsive behaviors by dynamically regulating self-assembly through sensing, processing, and transmitting environmental information. Emulating this is key to engineering dynamic synthetic materials with life-like functions. In most existing dynamic self-assembly systems, the responses are achieved by changes in the free energy landscape induced by external inputs (such as molecules, light, or pH) that push the system toward a new stable thermodynamic equilibrium. In contrast, achieving the sustained and complex processes characteristic of living systems requires a nonequilibrium approach involving continuous energy dissipation. Here, we present a new strategy for dynamic control of DNA origami tile self-assembly by directly coupling a transcriptional module's activity to the tiles' assembly state. Transcription is triggered only upon tile dimerization, which brings the module components into close proximity. The resulting RNA blocker strands then disassemble into dimers via strand displacement, establishing a dissipative, autonomous feedback loop. We demonstrated that integrating two mutually inhibitory tile pairs constructs a bistable system whose state can be switched by using RNA inducers or upstream transcriptional circuits. Simulations of larger networks further predict complex, nonequilibrium temporal behaviors (including sustained oscillations and pulses) that are maintained only through continuous energy consumption. This work presents a generalizable strategy for dynamic control of DNA origami tile self-assembly via transcriptional modules, paving the way for applications in nanorobotics, biosensing, biomedicine, and artificial life systems.