Transmetalation for DNA-Based Molecular Electronics.

The rational design of molecular electronics remains a grand challenge of materials science. DNA nanotechnology has offered unmatched control over molecular geometry, but direct electronic functionalization is a challenge. Here a generalized method is presented for tuning the local band structure of DNA using transmetalation in metal-mediated base pairs (mmDNA).

Precision Self-assembly of 3D DNA Crystals Using Microfluidics.

Controlling the uniformity in size and quantity of macroscopic three-dimensional (3D) DNA crystals is essential for their integration into complex systems and broader applications. However, achieving such control remains a major challenge in DNA nanotechnology. Here, we present a novel strategy for synthesizing monodisperse 3D DNA single crystals using microfluidic double-emulsion droplets as nanoliter-scale microreactors.

Silver(I)-Mediated 2D DNA Nanostructures.

Structural DNA nanotechnology enables the self-organization of matter at the nanometer scale, but approaches to expand the inorganic and electrical functionality of these scaffolds remain limited. Developments in nucleic acid metallics have enabled the incorporation of site-specific metal ions in DNA duplexes and provide a means of functionalizing the double helix with atomistic precision. Here a class of 2D DNA nanostructures that incorporate the cytosine-Ag-cytosine (dC:Ag:dC) base pair as a chemical trigger for self-assembly is described.

Six-Letter DNA Nanotechnology: Incorporation of - Base Pairs into Self-Assembling 3D Crystals.

Artificially expanded genetic information systems (AEGIS) were developed to expand the diversity and functionality of biological systems. Recent experiments have shown that these expanded DNA molecular systems are robust platforms for information storage and retrieval as well as useful for basic biotechnologies. In tandem, nucleic acid nanotechnology has seen the use of information-based "semantomorphic" encoding to drive the self-assembly of a vast array of supramolecular devices.

Engineering tertiary chirality in helical biopolymers.

Tertiary chirality describes the handedness of supramolecular assemblies and relies not only on the primary and secondary structures of the building blocks but also on topological driving forces that have been sparsely characterized. Helical biopolymers, especially DNA, have been extensively investigated as they possess intrinsic chirality that determines the optical, mechanical, and physical properties of the ensuing material. Here, we employ the DNA tensegrity triangle as a model system to locate the tipping points in chirality inversion at the tertiary level by X-ray diffraction.

Environmentally Controlled Oscillator with Triplex Guided Displacement of DNA Duplexes.

The use of DNA triplex association is advantageous for the reconfiguration of dynamic DNA nanostructures through pH alteration and can provide environmental control for both structural changes and molecular signaling. The combination of pH-induced triplex-forming oligonucleotide (TFOs) binding with toehold-mediated strand displacement has recently garnered significant attention in the field of structural DNA nanotechnology. While most previous studies use single-stranded DNA to displace or replace TFOs within the triplex, here we demonstrate that pH alteration allows a DNA duplex, with a toehold assistance, to displace TFOs from the components of another DNA duplex.

Heterobimetallic Base Pair Programming in Designer 3D DNA Crystals.

Metal-mediated DNA (mmDNA) presents a pathway toward engineering bioinorganic and electronic behavior into DNA devices. Many chemical and biophysical forces drive the programmable chelation of metals between pyrimidine base pairs. Here, we developed a crystallographic method using the three-dimensional (3D) DNA tensegrity triangle motif to capture single- and multi-metal binding modes across granular changes to environmental pH using anomalous scattering.

Metal-Mediated DNA Nanotechnology in 3D: Structural Library by Templated Diffraction.

DNA double helices containing metal-mediated DNA (mmDNA) base pairs are constructed from Ag and Hg ions between pyrimidine:pyrimidine pairs with the promise of nanoelectronics. Rational design of mmDNA nanomaterials is impractical without a complete lexical and structural description. Here, the programmability of structural DNA nanotechnology toward its founding mission of self-assembling a diffraction platform for biomolecular structure determination is explored.

Metal-Mediated DNA Nanotechnology in 3D: Structural Library by Templated Diffraction.

DNA double helices containing metal-mediated DNA (mmDNA) base pairs have been constructed from Ag and Hg ions between pyrimidine:pyrimidine pairs with the promise of nanoelectronics. Rational design of mmDNA nanomaterials has been impractical without a complete lexical and structural description. Here, we explore the programmability of structural DNA nanotechnology toward its founding mission of self-assembling a diffraction platform for biomolecular structure determination.

The Formation and Displacement of Ordered DNA Triplexes in Self-Assembled Three-Dimensional DNA Crystals.

Reconfigurable structures engineered through DNA hybridization and self-assembly offer both structural and dynamic applications in nanotechnology. Here, we have demonstrated that strand displacement of triplex-forming oligonucleotides (TFOs) can be translated to a robust macroscopic DNA crystal by coloring the crystals with covalently attached fluorescent dyes. We show that three different types of triplex strand displacement are feasible within the DNA crystals and the bound TFOs can be removed and/or replaced by (a) changing the pH from 5 to 7, (b) the addition of the Watson-Crick complement to a TFO containing a short toehold, and (c) the addition of a longer TFO that uses the duplex edge as a toehold.

Mesojunction-Based Design Paradigm of Structural DNA Nanotechnology.

Mesojunctions were introduced as a basic type of crossover configuration in the early development of structural DNA nanotechnology. However, the investigations of self-assembly from multiple mesojunction complexes have been overlooked in comparison to their counterparts based on regular junctions. In this work, we designed standardized component strands for the construction of complex mesojunction lattices.

The Rule of Thirds: Controlling Junction Chirality and Polarity in 3D DNA Tiles.

The successful self-assembly of tensegrity triangle DNA crystals heralded the ability to programmably construct macroscopic crystalline nanomaterials from rationally-designed, nanoscale components. This 3D DNA tile owes its "tensegrity" nature to its three rotationally stacked double helices locked together by the tensile winding of a center strand segmented into 7 base pair (bp) inter-junction regions, corresponding to two-thirds of a helical turn of DNA. All reported tensegrity triangles to date have employed turn inter-junction segments, yielding right-handed, antiparallel, "J1" junctions.

Programmable 3D Hexagonal Geometry of DNA Tensegrity Triangles.

Non-canonical interactions in DNA remain under-explored in DNA nanotechnology. Recently, many structures with non-canonical motifs have been discovered, notably a hexagonal arrangement of typically rhombohedral DNA tensegrity triangles that forms through non-canonical sticky end interactions. Here, we find a series of mechanisms to program a hexagonal arrangement using: the sticky end sequence; triangle edge torsional stress; and crystallization condition.

Highly Symmetric, Self-Assembling 3D DNA Crystals with Cubic and Trigonal Lattices.

The rational design of nanoscopic DNA tiles has yielded highly ordered crystalline matter in 2D and 3D. The most well-studied 3D tile is the DNA tensegrity triangle, which is known to self-assemble into macroscopic crystals. However, contemporary rational design parameters for 3D DNA crystals nearly universally invoke integer numbers of DNA helical turns and Watson-Crick (WC) base pairs.

Augmented DNA Nanoarchitectures: A Structural Library of 3D Self-Assembling Tensegrity Triangle Variants.

The DNA tensegrity triangle is known to reliably self-assemble into a 3D rhombohedral crystalline lattice via sticky-end cohesion. Here, the library of accessible motifs is expanded through covalent extensions of intertriangle regions and sticky-end-coordinated linkages of adjacent triangles with double helical segments using both geometrically symmetric and asymmetric configurations. The molecular structures of 18 self-assembled architectures at resolutions of 3.

The wending rhombus: Self-assembling 3D DNA crystals.

In this perspective, we provide a summary of recent developments in self-assembling three-dimensional (3D) DNA crystals. Starting from the inception of this subfield, we describe the various advancements in structure that have led to an increase in the diversity of macromolecular crystal motifs formed through self-assembly, and we further comment on the future directions of the field, which exploit noncanonical base pairing interactions beyond Watson-Crick. We then survey the current applications of self-assembling 3D DNA crystals in reversibly active nanodevices and materials engineering and provide an outlook on the direction researchers are taking these structures.

3D Hexagonal Arrangement of DNA Tensegrity Triangles.

The tensegrity triangle motif utilizes Watson-Crick sticky end cohesion to self-assemble into a rhombohedral crystal lattice using complementary 5'-GA and 5'-TC sticky ends. Here, we report that using noncanonical 5'-AG and 5'-TC sticky ends in otherwise isomorphic tensegrity triangles results in crystal self-assembly in the 6 hexagonal space group as revealed by X-ray crystallography. In this structure, the DNA double helices bend at the crossover positions, a feature that was not observed in the original design.

Reconfigurable Two-Dimensional DNA Lattices: Static and Dynamic Angle Control.

Branched DNA motifs serve as the basic construction elements for all synthetic DNA nanostructures. However, precise control of branching orientation remains a key challenge to further heighten the overall structural order. In this study, we use two strategies to control the branching orientation.

Construction and characterization of metal ion-containing DNA nanowires for synthetic biology and nanotechnology.

DNA is an attractive candidate for integration into nanoelectronics as a biological nanowire due to its linear geometry, definable base sequence, easy, inexpensive and non-toxic replication and self-assembling properties. Recently we discovered that by intercalating Ag in polycytosine-mismatch oligonucleotides, the resulting C-Ag-C duplexes are able to conduct charge efficiently. To map the functionality and biostability of this system, we built and characterized internally-functionalized DNA nanowires through non-canonical, Ag-mediated base pairing in duplexes containing cytosine-cytosine mismatches.