Designing a bio-responsive robot from DNA origami.

Nucleic acids are astonishingly versatile. In addition to their natural role as storage medium for biological information(1), they can be utilized in parallel computing(2,3) , recognize and bind molecular or cellular targets(4,5) , catalyze chemical reactions(6,7) , and generate calculated responses in a biological system(8,9). Importantly, nucleic acids can be programmed to self-assemble into 2D and 3D structures(10-12), enabling the integration of all these remarkable features in a single robot linking the sensing of biological cues to a preset response in order to exert a desired effect. Creating shapes from nucleic acids was first proposed by Seeman(13), and several variations on this theme have since been realized using various techniques(11,12,14,15) . However, the most significant is perhaps the one proposed by Rothemund, termed scaffolded DNA origami(16). In this technique, the folding of a long (>7,000 bases) single-stranded DNA 'scaffold' is directed to a desired shape by hundreds of short complementary strands termed 'staples'. Folding is carried out by temperature annealing ramp. This technique was successfully demonstrated in the creation of a diverse array of 2D shapes with remarkable precision and robustness. DNA origami was later extended to 3D as well(17,18) . The current paper will focus on the caDNAno 2.0 software(19) developed by Douglas and colleagues. caDNAno is a robust, user-friendly CAD tool enabling the design of 2D and 3D DNA origami shapes with versatile features. The design process relies on a systematic and accurate abstraction scheme for DNA structures, making it relatively straightforward and efficient. In this paper we demonstrate the design of a DNA origami nanorobot that has been recently described(20). This robot is 'robotic' in the sense that it links sensing to actuation, in order to perform a task. We explain how various sensing schemes can be integrated into the structure, and how this can be relayed to a desired effect. Finally we use Cando(21) to simulate the mechanical properties of the designed shape. The concept we discuss can be adapted to multiple tasks and settings.