Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra

DNA is renowned for its double helix structure and the base pairing that enables the recognition and highly selective binding of complementary DNA strands. These features, and the ability to create DNA strands with any desired sequence of bases, have led to the use of DNA rationally to design various nanostructures and even execute molecular computations. Of the wide range of self-assembled DNA nanostructures reported, most are one- or two-dimensional. Examples of three-dimensional DNA structures include cubes, truncated octahedra, octohedra and tetrahedra, which are all comprised of many different DNA strands with unique sequences. When aiming for large structures, the need to synthesize large numbers (hundreds) of unique DNA strands poses a challenging design problem. Here, we demonstrate a simple solution to this problem: the design of basic DNA building units in such a way that many copies of identical units assemble into larger three-dimensional structures. We test this hierarchical self-assembly concept with DNA molecules that form three-point-star motifs, or tiles. By controlling the flexibility and concentration of the tiles, the one-pot assembly yields tetrahedra, dodecahedra or buckyballs that are tens of nanometres in size and comprised of four, twenty or sixty individual tiles, respectively. We expect that our assembly strategy can be adapted to allow the fabrication of a range of relatively complex three-dimensional structures.     

Logical computation using algorithmic self-assembly of DNA triple-crossover molecules

Recent work has demonstrated the self-assembly of designed periodic two-dimensional arrays composed of DNA tiles, in which the intermolecular contacts are directed by 'sticky' ends. In a mathematical context, aperiodic mosaics may be formed by the self-assembly of 'Wang' tiles, a process that emulates the operation of a Turing machine. Macroscopic self-assembly has been used to perform computations; there is also a logical equivalence between DNA sticky ends and Wang tile edges. This suggests that the self-assembly of DNA-based tiles could be used to perform DNA-based computation. Algorithmic aperiodic self-assembly requires greater fidelity than periodic self-assembly, because correct tiles must compete with partially correct tiles. Here we report a one-dimensional algorithmic self-assembly of DNA triple-crossover molecules that can be used to execute four steps of a logical (cumulative XOR) operation on a string of binary bits.     

Folding DNA to create nanoscale shapes and patterns

'Bottom-up fabrication', which exploits the intrinsic properties of atoms and molecules to direct their self-organization, is widely used to make relatively simple nanostructures. A key goal for this approach is to create nanostructures of high complexity, matching that routinely achieved by 'top-down' methods. The self-assembly of DNA molecules provides an attractive route towards this goal. Here I describe a simple method for folding long, single-stranded DNA molecules into arbitrary two-dimensional shapes. The design for a desired shape is made by raster-filling the shape with a 7-kilobase single-stranded scaffold and by choosing over 200 short oligonucleotide 'staple strands' to hold the scaffold in place. Once synthesized and mixed, the staple and scaffold strands self-assemble in a single step. The resulting DNA structures are roughly 100 nm in diameter and approximate desired shapes such as squares, disks and five-pointed stars with a spatial resolution of 6 nm. Because each oligonucleotide can serve as a 6-nm pixel, the structures can be programmed to bear complex patterns such as words and images on their surfaces. Finally, individual DNA structures can be programmed to form larger assemblies, including extended periodic lattices and a hexamer of triangles (which constitutes a 30-megadalton molecular complex).     

3D DNA origami designed with caDNAno

For about three decades, DNA-based nanotechnology has been undergoing development as an assembly method for nanostructured materials. The DNA origami method pioneered by Rothemund paved the way for the formation of 3D structures using DNA self assembly. The origami approach uses a long scaffold strand as the input for the self assembly of a few hundred staple strands into desired shapes. Herein, we present a 3D origami "roller" (75 nm in length) designed using caDNAno software. This has the potential to be used as a template to assemble nanoparticles into different pre-defined shapes. The "roller" was characterized with agarose gel electrophoresis, atomic force microscopy (AFM) and transmission electron microscopy (TEM).     

最大匹配问题Tile自组装模型

Tile自组装模型凭借其自组装、可编程等特性在解决NP问题方面具有巨大优势.文中提出了一种求解最大匹配问题的Tile自组装新模型,该模型主要由初始配置子系统、选择子系统及检测子系统3大部分构成.新模型中首先设计Tile分子存储问题信息,其次通过Tile分子自组装操作生成最大匹配问题解空间,最后通过Tile检测分子筛选得到最大匹配问题的解.对模型从所需Tile分子种类、计算时间和计算空间3个方面进行性能分析,并通过实验模拟论证了模型的有效性和正确性.     

三维DNA自组装在多维背包问题中的应用研究

利用DNA自组装执行计算的思想已从实验上被证明了其可行性．已有多种理论模型被提出用以解决各种NP问题．基于DNA Tile自组装模型理论在二维下的扩展,本文设计了可以实现这一算法的三维DNA Tile组装系统,提出了一种用于解决多维背包问题的三维DNA自组装模型．该模型可以非确定性的输出可行性解决方案．分析表明系统可以在线性组装步骤内完成计算,所需的Tile种类数与问题维数无关．为探索三维DNA自组装的计算能力进行了一次有意义的尝试．     

基于DNA链置换反应的编码器逻辑运算模型研究

作为自组装DNA计算领域中一门新技术,DNA链置换反应在分子计算领域得到了广泛的应用.基于自组装DNA计算原理,设计了对应不同逻辑门的DNA分子电路.基于DNA链置换反应机理构建了编码器逻辑电路的分子计算模型.当输入DNA分子信号链时,将不同分子浓度比的DNA分子逻辑门电路混合,借助分子间的特异性杂交反应及分子间链置换反应,最终可输出信号链分子.Visual DSD仿真结果表明了本文设计的编码器逻辑计算模型的可行性与准确性.为拓展分子逻辑电路的应用做出有益的探索.     

Arithmetic computation using self-assembly of DNA tiles: subtraction and division

Recently,experiments have demonstrated that simple binary arithmetic and logical operations can be computed by the process of selfassembly of DNA tiles.In this paper,we show how the tile assembly process can be used for subtraction and division.In order to achieve this aim,four systems,including the comparator system,the duplicator system,the subtraction system,and the division system,are proposed to compute the difference and quotient of two input numbers using the tile assembly model.This work indicates that these systems can be carried out in polynomial time with optimal O(1)distinct tile types in parallel and at very low cost.Furthermore,we provide a scheme to factor the product of two prime numbers,and it is a breakthrough in basic biological operations using a molecular computer by self-assembly.     

Molecular logic computing model based on DNA self-assembly strand branch migration

In this study,the DNA logic computing model is established based on the methods of DNA self-assembly and strand branch migration.By adding the signal strands,the preprogrammed signals are released with the disintegrating of initial assembly structures.Then,the computing results are able to be detected by gel electrophoresis.The whole process is controlled automatically and parallely,even triggered by the mixture of input signals.In addition,the conception of single polar and bipolar is introduced into system designing,which leads to synchronization and modularization.Recognizing the specific signal DNA strands,the computing model gives all correct results by gel experiment.     

A molecular cryptography model based on structures of DNA self-assembly

With the progress of DNA computing, DNA- based cryptography becomes an emerging interdisciplinary research field. In this paper, we present a novel DNA cryptography that takes advantage of DNA self assembled structure. Making use of the toehold strands recognition and strand displacement, the bit-wise exclusive-or （XOR） operation is carried out to fulfill the information encryption and decryption in the form of a one-time-pad. The security of this system mainly comes from the physical isolation and specificity of DNA molecules. The system is con- structed by using complex DNA self-assembly, in which technique of fluorescent detection is utilized to implement the signal processing. In the proposed DNA cryptography, the XOR operation at each bit is carried out individually, thus the encryption and decryption process could be con- ducted in a massive, parallel way. This work may dem- onstrate that DNA cryptography has the great potential applications in the field of inRwmation security.     

通过DNA聚合剪切放大体系提高RNA的检测灵敏度

基于循环的DNA剪切循环放大分子机器构建了一个RNA传感器。该分子机器以RNA为输入,产生大量的DNA片段,并替换报告探针上的荧光DNA从而产生荧光信号,实现对靶RNA浓度的放大检测。本分子机器分为两部分,反应部分和报告部分。在反应部分,以靶RNA为输入条件,以一个特殊设计的探针为反应模板引发一个自发连续的DNA聚合-剪切反应网络,重复产生大量信号DNA链;这些信号DNA链进入报告部分,通过杂交替换反应从一个报告探针上替换下带有荧光DNA序列,释放到溶液中。这样通过剪切产生的大量DNA适体序列被释放到溶液中,并替换报告探针上的荧光DNA,实现信号的放大。     

Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli

When present in single-stranded DNA, palindromic or quasi-palindromic sequences have the potential to form complex secondary structures, including hairpins, which may facilitate interstrand misalignment of direct repeats and be responsible for diverse types of replication-based mutations, including deletions, additions, frameshifts and duplications. In regions of palindromic symmetry, specific deletion events may involve the formation of a hairpin or other DNA secondary structures which can stabilize the misalignment of direct repeats. One model suggests that these deletions occur during DNA replication by slippage of the template strand and misalignment with the progeny strand. The concurrent DNA replication model, involving an asymmetric dimeric DNA polymerase III complex which replicates the leading and lagging strands, has significant implications for mutagenesis. The intermittent looping of the lagging strand template, and the fact that the lagging strand template may contain a region of single-stranded DNA the length of an Okazaki fragment, provides an opportunity for DNA secondary-structure formation and misalignment. Here we report our design of a palindromic fragment to create an 'asymmetric palindromic insert' in the chloramphenicol acetyltransferase gene of plasmid pBR325. The frequency with which the insert was deleted in Escherichia coli depends on the orientation of the gene in the plasmid. Our results suggest that replication-dependent deletion between direct repeats may occur preferentially in the lagging strand.     

一种基于DNA自组装模型求解最大团问题的算法

基于tiles理论模型和已有DNA自组装模型,结合最大团问题给出基于DNA自组装模型的算法设计,得到具体设计初始分子、规则分子和检测分子所需的DAE块种类.在此基础上采用荧光标记和凝胶电泳生物操作提出了一种求解最大团问题算法.该算法设计tiles的种类为Θ(n2+|E|),其生物操作复杂性为Θ(1).此算法降低了实验的复杂度,而且保证了实验的易操作性和结果的准确性。     

刚性陶瓷瓦热防护系统概率设计分析方法

针对高超声速飞行器中广泛应用的陶瓷瓦热防护系统,结合有限元法和蒙特卡洛模拟建立了其概率热分析系统,提出了刚性陶瓷瓦热防护系统尺寸概率设计方法。建立了刚性陶瓷瓦热防护系统的二维有限元模型,考虑了热传导系数、比热容和表面辐射率等材料属性参数以及热防护系统各层厚度的不确定性,得到系统温度场的概率分布特性和系统热防护性能对各参数的灵敏度,并对系统的热可靠性进行了评估。算例表明:文中提出的方法对热防护系统设计过程中合理确定陶瓷瓦厚度和在保证系统性能的前提下有效减轻重量具有指导价值。     

墙地砖边缘检测与应用研究

以墙地砖为研究对象，给出了边缘提取算法，并用该算法对墙地砖进行了边缘提取，将该结果应用于智能墙地砖分栋机的软件编程中。     

A DNA-fuelled molecular machine made of DNA

Molecular recognition between complementary strands of DNA allows construction on a nanometre length scale. For example, DNA tags may be used to organize the assembly of colloidal particles, and DNA templates can direct the growth of semiconductor nanocrystals and metal wires. As a structural material in its own right, DNA can be used to make ordered static arrays of tiles, linked rings and polyhedra. The construction of active devices is also possible--for example, a nanomechanical switch, whose conformation is changed by inducing a transition in the chirality of the DNA double helix. Melting of chemically modified DNA has been induced by optical absorption, and conformational changes caused by the binding of oligonucleotides or other small groups have been shown to change the enzymatic activity of ribozymes. Here we report the construction of a DNA machine in which the DNA is used not only as a structural material, but also as 'fuel'. The machine, made from three strands of DNA, has the form of a pair of tweezers. It may be closed and opened by addition of auxiliary strands of 'fuel' DNA; each cycle produces a duplex DNA waste product.     

Reassembly of shattered chromosomes in Deinococcus radiodurans

Dehydration or desiccation is one of the most frequent and severe challenges to living cells. The bacterium Deinococcus radiodurans is the best known extremophile among the few organisms that can survive extremely high exposures to desiccation and ionizing radiation, which shatter its genome into hundreds of short DNA fragments. Remarkably, these fragments are readily reassembled into a functional 3.28-megabase genome. Here we describe the relevant two-stage DNA repair process, which involves a previously unknown molecular mechanism for fragment reassembly called 'extended synthesis-dependent strand annealing' (ESDSA), followed and completed by crossovers. At least two genome copies and random DNA breakage are requirements for effective ESDSA. In ESDSA, chromosomal fragments with overlapping homologies are used both as primers and as templates for massive synthesis of complementary single strands, as occurs in a single-round multiplex polymerase chain reaction. This synthesis depends on DNA polymerase I and incorporates more nucleotides than does normal replication in intact cells. Newly synthesized complementary single-stranded extensions become 'sticky ends' that anneal with high precision, joining together contiguous DNA fragments into long, linear, double-stranded intermediates. These intermediates require RecA-dependent crossovers to mature into circular chromosomes that comprise double-stranded patchworks of numerous DNA blocks synthesized before radiation, connected by DNA blocks synthesized after radiation.     

Self-assembly of two-dimensional DNA crystals

Self-assembly of synthetic oligonucleotides into two-dimensional lattices presents a 慴ottom-up?approach to the fabrication of devices on nanometer scale. We report the design and observation of two-dimensional crystalline forms of DNAs that are composed of twenty-one plane oligonucleo-tides and one phosphate-modified oligonucleotide. These synthetic sequences are designed to self-assemble into four double-crossover (DX) DNA tiles. The 憇ticky ends?of these tiles that associate according to WatsonCrick抯 base pairing are programmed to build up specific periodic patterns upto tens of microns. The patterned crystals are visualized by the transmission electron microscopy.     

DNA addition using linear self-assembly

This paper presents a DNA algorithm which adds two nonnegative binary integers using self-assembly in constant steps. The approach has the benefit of greater experimental simplicity when compared with previous DNA addition algorithms. For the addition of two binary n-bit integers, O（n） is different from DNA strands and only O（1） biochemical experimental procedures are required.