Three-Dimensional Structures Self-Assembled from DNA Bricks

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Science (Impact Factor: 33.61). 11/2012; 338(6111):1177-83. DOI: 10.1126/science.1227268
Source: PubMed


We describe a simple and robust method to construct complex three-dimensional (3D) structures by using short synthetic DNA
strands that we call “DNA bricks.” In one-step annealing reactions, bricks with hundreds of distinct sequences self-assemble
into prescribed 3D shapes. Each 32-nucleotide brick is a modular component; it binds to four local neighbors and can be removed
or added independently. Each 8–base pair interaction between bricks defines a voxel with dimensions of 2.5 by 2.5 by 2.7 nanometers,
and a master brick collection defines a “molecular canvas” with dimensions of 10 by 10 by 10 voxels. By selecting subsets
of bricks from this canvas, we constructed a panel of 102 distinct shapes exhibiting sophisticated surface features, as well
as intricate interior cavities and tunnels.

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Available from: Yonggang Ke, Apr 11, 2014
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    • "For example, Douglas and co-workers demonstrated the bottom-up design and assembly of DNA nanostructures with different shapes from monolith to square nut, railed bridge, genie bottle, stacked cross, and slotted cross with precisely controlled dimensions ranging from 10 nm to 100 nm[41]. In another typical case, Ke et al. described a simple and robust method to construct complex 3D DNA structures by using short synthetic DNA bricks[42]. Several review papers on the bottom-up synthesis and bioapplications of various DNA nanoshapes are recommended if the readers want to get more details44454647. "
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    ABSTRACT: The combination of nanotechnology, biology, and bioengineering greatly improved the developments of nanomaterials with unique functions and properties. Biomolecules as the nanoscale building blocks play very important roles for the final formation of functional nanostructures. Many kinds of novel nanostructures have been created by using the bioinspired self-assembly and the subsequent binding with various nanoparticles. In this review, we summarized the studies on the fabrications and sensor applications of biomimetic nanostructures. The strategies for creating different bottom-up nanostructures by using biomolecules like DNA, protein, peptide, and virus, as well as microorganisms like bacteria and plant leaf are introduced. In addition, the potential applications of the synthesized biomimetic nanostructures for colorimetry, fluorescence, surface plasmon resonance, surface-enhanced Raman scattering, electrical resistance, electrochemistry, and quartz crystal microbalance sensors are presented. This review will promote the understanding of relationships between biomolecules/microorganisms and functional nanomaterials in one way, and in another way it will guide the design and synthesis of biomimetic nanomaterials with unique properties in the future.
    Full-text · Article · Jan 2016 · Materials
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    • "Self-assembly is a widespread phenomenon that is observed across many biological, chemical, and physical systems . Examples include DNA [1] [2] [3] [4] [5] [6] [7], protein quaternary structure [8] [9], protein aggregation [10], viruses [11], micelles [12], and thin films [13], among others. In biology it is of particular importance as protein self-assembly gives rise to an enormous variety of molecular machinery in every living cell. "
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    ABSTRACT: Self-assembly is ubiquitous in nature, particularly in biology, where it underlies the formation of protein quaternary structure and protein aggregation. Quaternary structure assembles deterministically and performs a wide range of important functions in the cell, whereas protein aggregation is the hallmark of a number of diseases and represents a non-deterministic self-assembly process. Here we build on previous work on a lattice model of deterministic self-assembly to investigate non-deterministic self-assembly of single lattice tiles and mixtures of two tiles at varying relative concentrations. Despite limiting the simplicity of the model to two interface types, which results in 13 topologically distinct single tiles and 106 topologically distinct sets of two tiles, we observe a wide variety of concentration-dependent behaviours. Several two-tile sets display critical behaviours in form of a sharp transition from bound to unbound structures as the relative concentration of one tile to another increases. Other sets exhibit gradual monotonic changes in structural density, or non-monotonic changes, while again others show no concentration dependence at all. We catalogue this extensive range of behaviours and present a model that provides a reasonably good estimate of the critical concentrations for a subset of the critical transitions. In addition we show that the structures resulting from these tile sets are fractal, with one of two different fractal dimensions.
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    • "The use of DNA structures in biological and biomedical studies is particularly promising due to a number of advantages: DNA structures can be modified with a plethora of (bio)chemical moieties with nanoscale precision [7], there is full control over stoichiometry [8] [9], they are non-cytotoxic [10] [11], they can survive in cell media, blood serum and cultured cells for extended periods of time [12e14] and they can be used as carriers for immune-stimulatory motifs including unmethylated CpG sequences [10] [15]. Particularly the recently introduced DNA tile-assembly method [16] [17] could foster biomedical applications, as the tile-assembly method is extremely versatile, easy to apply, results in high yields of folded structures, and different than in DNA origami applications, no virus-derived scaffold is needed for assembly of DNA nanotubes. Unmethylated CpG sequences have immunogenic properties and are used as adjuvant in vaccination [18] or to overcome tumorassociated immunosuppression [19]. "
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    ABSTRACT: DNA-based nanoconstructs possess great potential for biomedical applications. However, the in vivo behavior of such constructs at the microscopic tissue/cell level as well as their inflammatory potential is largely unknown. Unmethylated CpG sequences of DNA are recognized by Toll-like receptor 9 (TLR9), and thus initiate an innate immune response. In this study, we investigated the use of DNA-based nanotubes as carrier systems for CpG delivery and their effect on immune cells in vivo and in real time. DNA nanotubes were microinjected into skeletal muscle of anesthetized mice. Using in vivo microscopy, we observed that the DNA tubes were internalized within minutes by tissue-resident macrophages and localized in their endosomes. Only microinjection of CpG-decorated DNA nanotubes but not of plain DNA nanotubes or CpG oligonucleotides induced a significant recruitment of leukocytes into the muscle tissue as well as activation of the NF-ĸB pathway in surrounding cells. These results suggest that DNA nanotubes are promising delivery vehicles to target tissue macrophages, whereupon the immunogenic potential depends on the decoration with CpG oligonucleotides. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · Biomaterials
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