DNA Lattices for the Study of Biological Processes

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DESCRIPTION (provided by applicant): This project will involve the preparation of DNA monomer building blocks that contain metal-ligand central hubs tethering either four or six DNA sequences. Self-assembly of these monomers by complementary hybridization generates supramolecular DNA nanoscale or mesoscale lattices. Lattices differ fundamentally from DNA dendrimers or other DNA assemblies since each monomer building block attaches to the growing supramolecular structure at more than one defined site. The result of lattice assembly is a regular array of DNA sequences, similar to a macroscopic crystal. Both tetrahedral (diamond) and octahedral (cubic) lattices will be characterized by x-ray diffraction methods in collaboration with Prof. Loren Williams (Georgia Tech). Surface-bound lattices will provide the opportunity to study a variety of binding events. Monolayers or multiple layers of the lattice can be generated bound to a gold surface through terminal thiol residues. In collaboration with Prof. Rosina Georgiadis (Boston University), we will be able to study the rates and extents of monolayer formation, as well as the rates and extents of ligand or protein binding to the surface-bound lattices. Through hybridization of appropriate conjugates, it will be possible to create surface arrays of bound biologicals as well as non-biologicals such as fluorophores, nanoparticles and quantum dots. The metal centers of the lattices can be viewed as functional sites that are spaced regularly by the presence of the DNA arms of the lattice. To study the properties of such metal arrays we will prepare light harvesting arrays based upon multiple antennae to capture photons and then monitor the energy transfer process to a central porphyrin or ruthenium center. In collaboration with Prof. Torsten Fiebig (Boston College) we will characterize the intermediates, lifetimes and efficiencies of these processes. Finally, the regular pore structure should permit the sequestering or the timed release of macroscale Pharmaceuticals or other agents. We will characterize the pore structure and determine how porous these materials are to selected macromolecules or nanoparticles