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Assembly of complex structures from a small set of tiles is a common theme in biology. For example, many copies of identical proteins make up polyhedron-shaped, viral capsids and tubulin can make long microtubules. This inspired the development of tile-based DNA self-assembly for nanoconstruction, particularly for structures with high symmetries. In the final structure, each type of motif will adopt the same conformation, either rigid or with defined flexibility. For structures that have no symmetry, their assembly remains a challenge from a small set of tiles. To meet this challenge, algorithmic self-assembly has been explored driven by computational science, but it is not clear how to implement this approach to one-dimensional (1D) structures. Here, we have demonstrated that a constant shift of a conformational equilibrium could allow 1D structures to evolve. As shown by atomic force microscopy imaging, one type of DNA tile successfully assembled into DNA spirals and concentric circles, which became less and less curved from the structure's center outward. This work points to a new direction for tile-based DNA assembly.more » « less
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Abstract Small, single‐stranded DNA (ssDNA) circles have many applications, such as templating rolling circle amplification (RCA), capturing microRNAs, and scaffolding DNA nanostructures. However, it is challenging to prepare such ssDNA circles, particularly when the DNA size becomes very small (e.g. a 20 nucleotide (nt) long ssDNA circle). Often, such short ssDNA dominantly form concatemers (either linear or circular) due to intermolecular ligation, instead of forming monomeric ssDNA circles by intramolecular ligation. Herein, a simple method to overcome this problem by designing the complementary linker molecules is reported. It is demonstrated that ssDNA, as short as 16 nts, can be enzymatically ligated (by the commonly used T4 DNA ligase) into monomeric ssDNA circles at high concentration (100 μM) with high yield (97 %). This method does not require any special sequence, thus, it is expected to be generally applicable. The experimental protocol is identical to regular DNA ligation, thus, is expected to be user friendly for general chemists and biologists.
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Abstract Small, single‐stranded DNA (ssDNA) circles have many applications, such as templating rolling circle amplification (RCA), capturing microRNAs, and scaffolding DNA nanostructures. However, it is challenging to prepare such ssDNA circles, particularly when the DNA size becomes very small (e.g. a 20 nucleotide (nt) long ssDNA circle). Often, such short ssDNA dominantly form concatemers (either linear or circular) due to intermolecular ligation, instead of forming monomeric ssDNA circles by intramolecular ligation. Herein, a simple method to overcome this problem by designing the complementary linker molecules is reported. It is demonstrated that ssDNA, as short as 16 nts, can be enzymatically ligated (by the commonly used T4 DNA ligase) into monomeric ssDNA circles at high concentration (100 μM) with high yield (97 %). This method does not require any special sequence, thus, it is expected to be generally applicable. The experimental protocol is identical to regular DNA ligation, thus, is expected to be user friendly for general chemists and biologists.
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Abstract DNA self‐assembly computation is attractive for its potential to perform massively parallel information processing at the molecular level while at the same time maintaining its natural biocompatibility. It has been extensively studied at the individual molecule level, but not as much as ensembles in 3D. Here, the feasibility of implementing logic gates, the basic computation operations, in large ensembles: macroscopic, engineered 3D DNA crystals is demonstrated. The building blocks are the recently developed DNA double crossover‐like (DXL) motifs. They can associate with each other via sticky‐end cohesion. Common logic gates are realized by encoding the inputs within the sticky ends of the motifs. The outputs are demonstrated through the formation of macroscopic crystals that can be easily observed. This study points to a new direction of construction of complex 3D crystal architectures and DNA‐based biosensors with easy readouts.
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Abstract Tile‐based DNA self‐assembly is a powerful approach for nano‐constructions. In this approach, individual DNA single strands first assemble into well‐defined structural tiles, which, then, further associate with each other into final nanostructures. It is a general assumption that the lower‐level structures (tiles) determine the higher‐level, final structures. In this study, we present concrete experimental data to show that higher‐level structures could, at least in the current example, also impact on the formation of lower‐level structures. This study prompts questions such as: how general is this phenomenon in programmed DNA self‐assembly and can we turn it into a useful tool for fine tuning DNA self‐assembly?