Inverse design of a pyrochlore lattice of DNA origami through model-driven experiments.

Sophisticated statistical mechanics approaches and human intuition have demonstrated the possibility of self-assembling complex lattices or finite-size constructs. However, attempts so far have mostly only been successful in silico and often fail in experiment because of unpredicted traps associated with kinetic slowing down (gelation, glass transition) and competing ordered structures. Theoretical predictions also face the difficulty of encoding the desired interparticle interaction potential with the experimentally available nano- and micrometer-sized particles. To overcome these issues, we combine SAT assembly (a patchy-particle interaction design algorithm based on constrained optimization) with coarse-grained simulations of DNA nanotechnology to experimentally realize trap-free self-assembly pathways. We use this approach to assemble a pyrochlore three-dimensional lattice, coveted for its promise in the construction of optical metamaterials, and characterize it with small-angle x-ray scattering and scanning electron microscopy visualization.

High-Affinity Host-Guest Recognition for Efficient Assembly and Enzymatic Responsiveness of DNA Nanostructures.

The combination of multiple orthogonal interactions enables hierarchical complexity in self-assembled nanoscale materials. Here, efficient supramolecular polymerization of DNA origami nanostructures is demonstrated using a multivalent display of small molecule host-guest interactions. Modification of DNA strands with cucurbit[7]uril (CB[7]) and its adamantane guest, yielding a supramolecular complex with an affinity of order 1010 m-1 , directs hierarchical assembly of origami monomers into 1D nanofibers. This affinity regime enables efficient polymerization; a lower-affinity ß-cyclodextrin-adamantane complex does not promote extended structures at a similar valency. Finally, the utility of the high-affinity CB[7]-adamantane interactions is exploited to enable responsive enzymatic actuation of origami nanofibers assembled using peptide linkers. This work demonstrates the power of high-affinity CB[7]-guest recognition as an orthogonal axis to drive self-assembly in DNA nanotechnology.

Bioactive Fibronectin-III10-DNA Origami Nanofibers Promote Cell Adhesion and Spreading.

The integration of proteins with DNA nanotechnology would enable materials with diverse applications in biology, medicine, and engineering. Here, we describe a method for the incorporation of bioactive fibronectin domain proteins with DNA nanostructures using two orthogonal coiled-coil peptides. One peptide from each coiled-coil pair is attached to a DNA origami cuboid in a multivalent fashion by attaching the peptides to DNA handles. These structures can then be assembled into one-dimensional arrays through the addition of a fibronectin domain linker genetically fused with the complementary peptides to those on the origami. We validate array formation using two different self-assembly protocols and characterize the fibers by atomic force and electron microscopy. Finally, we demonstrate that surfaces coated with the protein-DNA nanofibers can serve as biomaterial substrates for fibroblast adhesion and spreading with the nanofibers showing enhanced bioactivity compared to that of the monomeric protein.

Coarse-Grained Simulations for the Characterization and Optimization of Hybrid Protein-DNA Nanostructures.

We present here the combination of experimental and computational modeling tools for the design and characterization of protein-DNA hybrid nanostructures. Our work incorporates several features in the design of these nanostructures: (1) modeling of the protein-DNA linker identity and length; (2) optimizing the design of protein-DNA cages to account for mechanical stresses; (3) probing the incorporation efficiency of protein-DNA conjugates into DNA nanostructures. The modeling tools were experimentally validated using structural characterization methods like cryo-TEM and AFM. Our method can be used for fitting low-resolution electron density maps when structural insights cannot be deciphered from experiments, as well as enable in-silico validation of nanostructured systems before their experimental realization. These tools will facilitate the design of complex hybrid protein-DNA nanostructures that seamlessly integrate the two different biomolecules.

Structural DNA Nanotechnology: Immobile Holliday Junctions to Artifi.

DNA nanotechnology marvels the scientific world with its capabilities to design, engineer, and demonstrate nanoscale shapes. This review is a condensed version walking the reader through the structural developments in the field over the past 40 years starting from the basic design rules of the double-stranded building block to the most recent advancements in self-assembled hierarchically achieved structures to date. It builds from the fundamental motivation of building 3-dimensional (3D) lattice structures of tunable cavities going all the way up to artificial nanorobots fighting cancer. The review starts by covering the most important developments from the fundamental bottom-up approach of building structures, which is the 'tile' based approach covering 1D, 2D, and 3D building blocks, after which the top-down approach using DNA origami and DNA bricks is also covered. Thereafter, DNA nanostructures assembled using not so commonly used (yet promising) techniques like i-motifs, quadruplexes, and kissing loops are covered. Highlights from the field of dynamic DNA nanostructures have been covered as well, walking the reader through various approaches used within the field to achieve movement. The article finally concludes by giving the authors a view of what the future of the field might look like while suggesting in parallel new directions that fellow/future DNA nanotechnologists could think about.

Programming nanoparticle valence bonds with single-stranded DNA encoders.

Nature has evolved strategies to encode information within a single biopolymer to program biomolecular interactions with characteristic stoichiometry, orthogonality and reconfigurability. Nevertheless, synthetic approaches for programming molecular reactions or assembly generally rely on the use of multiple polymer chains (for example, patchy particles). Here we demonstrate a method for patterning colloidal gold nanoparticles with valence bond analogues using single-stranded DNA encoders containing polyadenine (polyA). By programming the order, length and sequence of each encoder with alternating polyA/non-polyA domains, we synthesize programmable atom-like nanoparticles (PANs) with n-valence that can be used to assemble a spectrum of low-coordination colloidal molecules with different composition, size, chirality and linearity. Moreover, by exploiting the reconfigurability of PANs, we demonstrate dynamic colloidal bond-breaking and bond-formation reactions, structural rearrangement and even the implementation of Boolean logic operations. This approach may be useful for generating responsive functional materials for distinct technological applications.

Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks.

Three-dimensional (3D) cages are one of the most important targets for nanotechnology. Both proteins and DNA have been used as building blocks to create tunable nanoscale cages for a wide range of applications, but each molecular type has its own limitations. Here, we report a cage constructed from both protein and DNA building blocks through the use of covalent protein-DNA conjugates. We modified a homotrimeric protein (KDPG aldolase) with three identical single-stranded DNA handles by functionalizing a reactive cysteine residue introduced via site-directed mutagenesis. This protein-DNA building block was coassembled with a triangular DNA structure bearing three complementary arms to the handles, resulting in tetrahedral cages comprising six DNA sides capped by the protein trimer. The dimensions of the cage could be tuned through the number of turns per DNA arm (3 turns ∼ 10 nm, 4 turns ∼ 14 nm), and the hybrid structures were purified and characterized to confirm the three-dimensional structure. Cages were also modified with DNA using click chemistry and using aldolase trimers bearing the noncanonical amino acid 4-azidophenylalanine, demonstrating the generality of the method. Our approach will allow for the construction of nanomaterials that possess the advantages of both protein and DNA nanotechnology and find applications in fields such as targeted delivery, structural biology, biomedicine, and catalytic materials.

Layered-Crossover Tiles with Precisely Tunable Angles for 2D and 3D DNA Crystal Engineering.

DNA tile-based assembly provides a promising bottom-up avenue to create designer two-dimensional (2D) and three-dimensional (3D) crystalline structures that may host guest molecules or nanoparticles to achieve novel functionalities. Herein, we introduce a new kind of DNA tiles (named layered-crossover tiles) that each consists of two or four pairs of layered crossovers to bridge DNA helices in two neighboring layers with precisely predetermined relative orientations. By providing proper matching rules for the sticky ends at the terminals, these layered-crossover tiles are able to assemble into 2D periodic lattices with precisely controlled angles ranging from 20° to 80°. The layered-crossover tile can be slightly modified and used to successfully assemble 3D lattice with dimensions of several hundred micrometers with tunable angles as well. These layered-crossover tiles significantly expand the toolbox of DNA nanotechnology to construct materials through bottom-up approaches.

Luminescent microporous metal-organic framework with functional lewis basic sites on the pore surface: specific sensing and removal of metal ions.

A three-dimensional luminescent metal-organic framework, {Mg(DHT)(DMF)(2)}(n) (1), based on an excited-state intramolecular proton-transfer (ESIPT) responsive linker, 2,5-dihydroxyterephthalic acid (H(2)DHT), has been synthesized, and its desolvated microporous framework with pendent -OH groups on the pore surface was exploited for the binding and specific sensing of metal ions via Lewis acid-base interactions. The luminescence intensity significantly quenches with Cu(II) among various s- and d-block metal ions, and highly selective sensing of Cu(II) ions has been realized in both solid and solution states (up to nanomolar concentration). The immobilized Cu(II) metal ions can be selectively removed by chelating agents like ethylenediaminetetraacetic acid without any structural disintegration of the framework, as revealed by the luminescence and gas-adsorption studies.