Programmable DNA Lattices: Design Synthesis and Applications

Recent Contract Accomplishments: Fall, 2001

This is a new start: the contract was activated in September, 2001.

We have hired further personnel (graduate students and staff) and improved computational and experimental facilities.

Began investigation of various assembly techniques for patterned 1D and 2D DNA lattices of moderate length, using techniques of unmediated algorithmic self-assembly, step-wise assembly, and directed nucleation assembly. We have identified strategies for patterning surfaces at the nanometer scale, including patterns required for nanoelectronic circuits, such as a RAM memory array and addressing circuits. We will soon move this project toward experimental realization using algorithmic DNA self-assembly.

Achieved visualization of self-assembled DNA nanostructures by platinum rotary shadowing on transmission electron microscopy (TEM), yielding higher resolution images of DNA lattice than any previously available from atomic force microscopy (AFM), including the ability to visualize individual tiles.

We designed and crystallized four different 3D periodic DX DNA lattices; these are the first examples of designed 3D macromolecular crystals. Performed diffraction studies at the NSLS synchrotron indicate 10 Å resolution for the trigonal DX motif, 7.5 Å resolution for the triclinic TX motif (but in a twinned crystal), and no diffraction for the others. Re-designed the motifs for a combinatorial scan, to optimize the choice of periodicity of DNA to use, so as to remove the system from the constraint of using only those periodicities that are most stable in solution, rather than in the target solid state. Begun characterization of the melting behavior of these DNA motif assemblies by dynamic light scattering (DLS) in a temperature-controlled system, with the goal of determining the best temperature at which to examine crystallization.

We constructed tube-like filaments of DNA lattice constructed from DNA tiles with the addition of thiol and amino groups to opposite sides of DNA tiles; these DNA filaments still have sticky-ends available at both ends which can be used for orienting the entire filament prior to metal binding. Achieved targeted metallization of these filaments of DNA lattice, using (i) nanogold targeted to the amino groups on the protruding DNA stem and (ii) a silver enhancement procedure which deposits silver upon existing bound gold particles; progressive build-up of metal atoms was observed, which is a step toward the goal of forming a complete, conductive wire.

Began development of a mathematical/algorithmic framework for design of multi-strand DNA structures. We have begun to formulate the DNA design problem in terms of partition functions for multi-stranded DNA complexes, to examine tractable models of DNA pseudo-knots, and to develop software for specifying and creating 3D molecular models of DNA structures. Began design of nucleating structures for de-multiplexing RAM lattice. We also improved existing software for design of DNA nanostructures and their DNA sequences and tested that software for the design of improved triple-crossover and single-strand DNA tiles.