CONSPECTUS: In recent decades, DNA has taken on an assortment of diverse roles, not only as the central genetic molecule in biological systems but also as a generic material for nanoscale engineering. DNA possesses many exceptional properties, including its biological function, biocompatibility, molecular recognition ability, and nanoscale controllability. Taking advantage of these unique attributes, a variety of DNA materials have been created with properties derived both from the biological functions and from the structural characteristics of DNA molecules. These novel DNA materials provide a natural bridge between nanotechnology and biotechnology, leading to far-ranging real-world applications. In this Account, we describe our work on the design and construction of DNA materials. Based on the role of DNA in the construction, we categorize DNA materials into two classes: substrate and linker. As a substrate, DNA interfaces with enzymes in biochemical reactions, making use of molecular biology's "enzymatic toolkit". For example, employing DNA as a substrate, we utilized enzymatic ligation to prepare the first bulk hydrogel made entirely of DNA. Using this DNA hydrogel as a structural scaffold, we created a protein-producing DNA hydrogel via linking plasmid DNA onto the hydrogel matrix through enzymatic ligation. Furthermore, to fully make use of the advantages of both DNA materials and polymerase chain reaction (PCR), we prepared thermostable branched DNA that could remain intact even under denaturing conditions, allowing for their use as modular primers for PCR. Moreover, via enzymatic polymerization, we have recently constructed a physical DNA hydrogel with unique internal structure and mechanical properties. As a linker, we have used DNA to interface with other functional moieties, including gold nanoparticles, clay minerals, proteins, and lipids, allowing for hybrid materials with unique properties for desired applications. For example, we recently designed a DNA-protein conjugate as a universal adapter for protein detection. We further demonstrate a diverse assortment of applications for these DNA materials including diagnostics, protein production, controlled drug release systems, the exploration of life evolution, and plasmonics. Although DNA has shown great potential as both substrate and linker in the construction of DNA materials, it is still in the initial stages of becoming a well-established and widely used material. Important challenges include the ease of design and fabrication, scaling-up, and minimizing cost. We envision that DNA materials will continue to bridge the gap between nanotechnology and biotechnology and will ultimately be employed for many real-world applications.

Highly ordered arrays of nanoparticles exhibit many properties that are not found in their disordered counterparts. However, these nanoparticle superlattices usually form in a far-from-equilibrium dewetting process, which precludes the use of conventional patterning methods owing to a lack of control over the local dewetting dynamics. Here, we report a simple yet efficient approach for patterning such superlattices that involves moulding microdroplets containing the nanoparticles and spatially regulating their dewetting process. This approach can provide rational control over the local nucleation and growth of the nanoparticle superlattices. Using DNA-capped gold nanoparticles as a model system, we have patterned nanoparticle superlattices over large areas into a number of versatile structures with high degrees of internal order, including single-particle-width corrals, single-particle-thickness microdiscs and submicrometre-sized 'supra-crystals'. Remarkably, these features could be addressed by micropatterned electrode arrays, suggesting potential applications in bottom-up nanodevices.

In most contemporary life forms, the confinement of cell membranes provides localized concentration and protection for biomolecules, leading to efficient biochemical reactions. Similarly, confinement may have also played an important role for prebiotic compartmentalization in early life evolution when the cell membrane had not yet formed. It remains an open question how biochemical reactions developed without the confinement of cell membranes. Here we mimic the confinement function of cells by creating a hydrogel made from geological clay minerals, which provides an efficient confinement environment for biomolecules. We also show that nucleic acids were concentrated in the clay hydrogel and were protected against nuclease, and that transcription and translation reactions were consistently enhanced. Taken together, our results support the importance of localized concentration and protection of biomolecules in early life evolution, and also implicate a clay hydrogel environment for biochemical reactions during early life evolution.

The crystallization of organically capped nanoparticles, unlike the hard-sphere crystallization of atoms, molecules, or conventional colloids, is a "soft process" in which the deformation of organic layers (soft coronae) unavoidably occurs. Despite previous efforts that focused mainly on structures at thermodynamic equilibrium, [1][2][3][4][5][6][7][8][9][10][11] it is not known how soft coronae deform dynamically in this soft-crystallization process. Here, using DNA-capped nanoparticles as a model system, we have probed in real time and in situ the entire drying-mediated soft-crystallization process by synchrotronbased small-angle X-ray scattering (SAXS). Notably, in our DNA-based approach [10,11] the known strategy of programmable crystal formation [12][13][14] is combined with drying-mediated self-assembly. [15] Our dynamic studies demonstrate that our soft crystals have continuously scalable crystalline states with a gradual transition from "wet crystals" to "dry crystals". We have found that the drying-mediated deformation of DNA molecules is elastic in accordance with an entropic spring model, which can also be applied in general to the drying-mediated self-assembly of other organically capped inorganic nanoparticles.We define the softness of the soft-corona/solid-core particle by the dimensionless quantity c = 2 h 0 /d core , where h 0 is the effective height of the corona layer and d core is the diameter of the nanoparticle core (Figure 1). Compared to alkyl-chain-derivatized nanoparticles, [1][2][3][4][5]7] DNA-capped nanoparticles are much softer spheres. Based on our definition, we obtain a typical softness of 0.3-0.8 for alkyl-corona nanoparticles [16] and a softness of 0.6-5.1 for our DNA-corona nanoparticles (these consist of nanoparticles 13 nm in diameter end-grafted with single-stranded DNA (ssDNA) 5 to 90 bases in length). In contrast to the crystallization of colloidal hard spheres (c = 0), the drying-mediated stress that water imparts on the nanoparticles can lead to the deformation of soft-corona nanoparticles (c > 0). This stress is derived from surface tension, which increases with water evaporation. [17] We mapped comprehensively (both temporally and spatially) the crystallization events of different DNAcapped nanoparticles over the entire lifetime of a drying droplet by means of real-time and in situ synchrotron-based SAXS. One-dimensional (1D) SAXS data (structure factor S(q) versus scattering vector q; for details see the Supporting Information) was used to index crystalline lattices and quantitatively determine the nearest-neighbor spacing, D NN . We first showed that nanoparticle supracrystals form for all DNA sequences investigated (see Section 1 in the Supporting Information), regardless of whether the sequences contain Watson-Crick base-pairing regions. However, the crystallization time, t c , at which supracrystals start to form, varies between sequences. We compared time-lapse 2D SAXS images from the entire drying periods for 5'-TGTAC and [*] Dr.

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