Supramolecular DNA Structures: From Design to Function

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Our research during the last 6 years has led to several discoveries in the fields of supramolecular chemistry and DNA nanotechnology. These include:(a) DNA cages that encapsulate therapeutics and release them selectively, only when they encounter a molecule that is present in cancer cells, and that have favorable in vitro and in vivo properties of these structures. (b) the observation that DNA nanostructures can be used as a temporary “printing press” rather than a permanent scaffold, and can transfer their structural information to gold particles and polymers. This introduces the notion that supramolecular information can be chemically transmitted from one material to another. (c) an alternative method to expand the DNA base-pairing code, by adding a small hydrogen-bonding molecule that reprograms DNA base-pairing into a “rosette” motif.(d) a new class of polymers which are monodisperse and sequence-controlled, synthesized by adapting the tools of automated solid-phase DNA synthesis. Combining them with DNA nanostructures leads to emergent assembly modes which could not have been obtained by either material.(e) the building of complex DNA structures by controlling the order of addition of their components which can then be re-used, thus using temporal control to achieve complexity. This proposal describes the use of DNA assembly to bring unprecedented structural definition and dynamic character to two important classes of materials: synthetic polymers and lipid bilayers. Interaction of DNA nanostructures with lipid bilayer membranes. DNA cages have tremendous potential for sensing, imaging, and drug delivery applications. The first interface that they encounter when they interact with cells are lipid bilayer membranes, and thus understanding this process is essential to transition them to biological applications. In this proposal, we examine the interaction of DNA nanostructures with lipid bilayers and develop two applications for these materials: as membrane nanopores for biomolecule detection, and as rafts' to mediate cell attachment and tune membrane curvature.Molecular “Printing” on Polymers with DNA Structures. We will build upon our recent discovery that DNA nanostructures can be used as a temporary template, or a “printing press”. There has been tremendous interest and elegant methods to increase the complexity of polymer nanostructures. However, the structural definition of DNA and its programmability are unmatched in polymer chemistry. We will describe the use of DNA structures as templates to covalently attach DNA patterns to polymeric nanoparticles in 2D- and 3D-, and to control their size and shape with DNA molding' strategies. This results in unprecedented polymer particles that assemble in a directional manner, the way that atoms come together to make molecules, thus dramatically increasing the level of control and programmability in polymer self-assembly.