Programmable DNA Lattices: Design Synthesis and Applications

Approach:

The recent development (both theoretical and experimental) of self-assembled DNA nanostructures provide a methodology for bottom-up nanoscale construction of highly patterned systems. These utilize macromolecular building blocks (DNA tiles) based on branched DNA. The methodology of DNA self-assembly begins with the artificial synthesis of single stranded DNA molecules, which self-assemble into DNA tiles, which further self-assemble into large structures with molecular-scale features. These DNA tiles have sticky ends that preferentially match the sticky ends of particular other DNA tiles, facilitating the further assembly into 1D, 2D and 3D tiling lattices. The DNA lattices are nanometer-scale. They may be periodic and aperiodic depending on the DNA tiles. (See the review paper http://www.cs.duke.edu/~reif/paper/SELFASSEMBLE/selfassemble.pdf .)

This methodology is programmable in the sense that in principle, by the appropriate choice of the set of DNA tiles, the DNA tiling assemblies can be made to form any computable 2D or 3D pattern, however complex, by the appropriate choice of the component DNA of the tiles. Hence the DNA tile assembly technique is the most advanced and versatile system known for programmable construction on the nanoscale.

This project combines the strengths of the leading research groups in DNA lattices: Duke (Reif), NYU (Seeman), and Caltech (Winfree). Previously our teams at Duke, NYU and Caltech have experimentally demonstrated 1D periodic tilings, a 1D DNA tiling assembly that can execute computations, as well as 2D DNA tiling assemblies forming large periodic 2D lattices from a variety of tile motifs.

This research project extends our prior experimental techniques in various ways with the goal of assembling for the first time: DNA lattices with 2D complex patterning, and periodic 3D DNA lattices. The work includes the development of new designs for DNA nanostructures, new structural motifs for DNA lattices, novel attachment chemistries enabling nano-patterning of a wide range of materials on DNA lattices, software to assist the design and simulation of DNA nanostructures, and demonstrations of various applications.

Our DNA lattices provide a highly flexible nanostructure construction methodology: by selectively attaching various other types of molecules to the tiles of the lattices, these lattices can be used as superstructure scaffolding for placement of nanocomponents composed of a wide variety of other materials, for example proteins, molecular electronics and robotics components. The programmability of self-assembled DNA lattices allows for this scaffolding to have patterning as required for fabrication of complex devices composed of these components.

One of our challenge problems is to construct a periodic 3D DNA lattices of sufficient regularity and size to be used for X-ray crystallography applications (for aligning proteins for X-ray diffraction). Our further challenge problem, demonstrating the self-assembly of patterned 2D DNA lattices, is the self-assembly of the pattern for a demultiplexed RAM circuit.