(699b) Photo-Triggered Self-Assembly and Actuation of DNA Nanostructures and Machines Using Photocaged Nucleotides

DNA nanotechnology has emerged as one of the most powerful methods for constructing complex nanoscale devices with precise addressability. The ability to actuate these devices on-demand would provide a powerful method for creating dynamic nanomachines that can reconfigure nanostructures, apply precisely defined forces, or spatiotemporally control self-assembly. Typically, DNA nanostructures have been dynamically modulated by either incorporating photoswitchable azobenzene nucleotides that, while effective, often suffer from slow kinetics and undesired reversibility. Another approach involves adding displacement strands that can bind to toehold regions and out-compete other interactions to change the state of a nanostructure. However, this approach is limited by the need to add an exogenous strand, which is not feasible for many applications, especially in biology. To circumvent these limitations, we have developed a series of photo-cleavable oligonucleotides that block hybridization until illuminated with UV light. By incorporating caged displacement strands within an existing nanostructure, we can prevent their action until illuminated. These strands serve as effective "internal toeholds" that can be activated on-demand. We have constructed a number of one-, two-, and three-dimensional assemblies that can form only upon irradiation, as well as a nanomechanical tweezer that switches between the closed and open state with UV light. In effect, this device can apply a nanomechanical force within a few seconds of illumination, paving the way for dynamic nanomachines that can exert controlled motion. We will also describe the design principles for more complex nanostructures that can find applications in targeted drug delivery or reconfiguration inside cells to influence biological processes.