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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    • "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.
    Biomaterials 06/2015; 53. DOI:10.1016/j.biomaterials.2015.02.099 · 8.56 Impact Factor
    • "The DNA double helix is stabilized by hydrogen bonds formed by complementary nucleotide bases and by the stacking of adjacent bases [2]. The remarkable specificity and robustness of these assemblies has inspired the engineering of several sophisticated structures, through single-stranded DNA self-assembly [3] [4]. Cell membranes are mainly composed of phospholipids, which self-assemble into lipid bilayers. "
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    ABSTRACT: Molecular self-assembly is a process ubiquitous in nature that refers to the spontaneous assembly of molecules in order to generate supramolecular structures through noncovalent interactions. Such a natural mechanism can be mimicked to modulate the fabrication of novel materials. The secret underlying the production of successful self-assembled materials lies on the careful selection of its building blocks. Control over the final architecture may be achieved by adjusting the size, shape and surface chemistry of these building blocks. Peptides are promising candidates as monomers for self-assembly, in part, due to the variety of amino acids which comprise different chemical functionalities. Such chemical diversity allows several interactions to take place, such as hydrogen bonding, hydrophobic effects or electrostatic interactions. In addition to design versatility, an increasing understanding of protein and peptide folding mechanisms allows the rational design of the monomer and its final assembly. Peptides have great potential for biomedical applications due to their inherent biocompatibility and biodegradability. In fact, self-assembled peptide-based biomaterials have been developed for the production of 3D scaffolds for tissue repair and regeneration and therapeutic drug delivery. Since peptides are bioactive molecules, its applications may go far beyond the fabrication of inactive architectures. Inherently functional materials may also be produced. In this review, we explore the different strategies adopted by scientists in the fabrication of peptide-based self-assembled biomaterials and provide a comprehensive overview of the mechanisms governing it.
    Current Organic Chemistry 06/2015; 19(999):1-1. DOI:10.2174/1385272819666150608220036 · 2.16 Impact Factor
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