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Reconfiguration of DNA molecular arrays driven by information relay
Science ( IF 44.7 ) Pub Date : 2017-06-22 , DOI: 10.1126/science.aan3377
Jie Song 1, 2 , Zhe Li 3 , Pengfei Wang 1 , Travis Meyer 1 , Chengde Mao 3 , Yonggang Ke 1, 4
Affiliation  

Relaying information on DNA tiles Arrays of modular DNA units can relay information by transforming their internal shape in response to binding of DNA trigger strands. Song et al. synthesized rectangular arrays of double-stranded DNA (see the Perspective by Yang and Lin). Transient square configurations transform into two stable rectangular structures by pinching across a pair of opposing vertices. Binding of DNA trigger strands causes switching into the alternative stable configuration. The tiles thus create a cascade of transformations along a particular pathway, thereby transmitting information about where binding occurred. Science, this issue p. eaan3377; see also p. 352 Transformation of DNA arrays is guided by pathways of information propagation among the interconnected molecular units. INTRODUCTION Information relay at the molecular level is an essential phenomenon in numerous chemical and biological processes. A key challenge in synthetic molecular self-assembly is to construct artificial structures that imitate these complex dynamic behaviors in controllable systems. One promising route is DNA self-assembly, a potent approach for the design and construction of arbitrary-shaped artificial nanostructures with increasing complexity and precision. Nonetheless, despite recent progress in the construction of reconfigurable DNA nanostructures that undergo tailored postassembly transformations in response to different physical or chemical cues, the dynamic behaviors of massive, complex DNA structures remain limited. The existing systems typically exhibit relatively simple dynamic behaviors that involve a single step or a few steps of transformation. Moreover, many of these structures contain mainly static segments joined by a few small reconfigurable domains. RATIONALE Here, we demonstrated prescribed, long-range information relay in artificial molecular arrays assembled from modular DNA antijunction units. The small dynamic antijunction unit contains four DNA double-helix domains of equal length and four dynamic nicking points, and can switch between two stable conformations, through an intermediate open conformation. In an array, the driving force of information relay is base stacking: The conformational switch of one antijunction unit will cause the interface between the transformed unit and its neighboring units to become a high-energy conformation with weakened base stacking, leading to transformations in the neighboring units. The array transformation is equivalent to a molecular “domino array”: Once initiated at a few selected units, the transformation then propagates, without the addition of extra “trigger strands,” to neighboring units and eventually the entire array. The specific information pathways by which this transformation occurs can be controlled by adding trigger strands to specific units, or by altering the design of individual units, the connections between units, and the geometry of the array. RESULTS The reconfigurable DNA relay arrays were constructed by using both origami and single-strand–brick approaches. In one-pot assembly, we observed that the arrays built from antijunction units exhibited a spectrum of shapes to accommodate different combinations of antijunction conformations. With the incorporation of set strands, we could lock the arrays into prescribed conformations. The more set strands were added, the greater the assembly shifted toward the corresponding array conformation. Other factors, including the size and aspect ratio of an array, the connecting pattern of an array, DNA sequences of an array, cation concentration, and temperature, have been shown to affect the result of one-pot assembly. The transformation cascade was demonstrated with preassembled arrays. When starting from one conformation, addition of the trigger strand at selected locations of the array initiates structural transformation from the selected sites and propagates to the rest of the array in a stepwise manner without additional trigger strands at other locations. Releasing the old trigger strands and adding new ones can transform the array back to its initial conformation—a reversible process that can be repeated multiple rounds. In addition, we were able to control the propagation pathway to follow prescribed routes, as well as to stop and then resume propagation by mechanically decoupling the antijunctions or introducing “block strands.” The kinetics of array transformation can be enhanced by elevated temperature or formamide. These assembly and transformations were studied mainly by atomic force microscopy and native agarose gel electrophoresis. CONCLUSION Our work demonstrates controlled, multistep, long-range transformation in DNA nanoarrays, assembled by interconnected modular dynamic units that can transfer their structural information to neighbors. The array’s dynamic behavior can be regulated by external factors, the shapes and sizes of arrays, the initiation of transformation at selected units, and the engineered information propagation pathways. We expect that the DNA relay arrays will shed new light on how to construct nanostructures with increasing size and complex dynamic behaviors, and may enable a range of applications, such as the construction of molecular devices to detect and translate molecular interactions to conformational changes in DNA structures, to remotely trigger subsequent molecular events. Information relay in DNA “domino” nanoarrays. In a manner similar to that of domino arrays (top), the molecular DNA nanoarray transforms in a step-by-step relay process, initiated by the hybridization of a trigger strand to a single unit (middle). Different stages of nanoarray transformation were confirmed by AFM (bottom). Scale bar, 50 nm. Information relay at the molecular level is an essential phenomenon in numerous chemical and biological processes, such as intricate signaling cascades. One key challenge in synthetic molecular self-assembly is to construct artificial structures that imitate these complex behaviors in controllable systems. We demonstrated prescribed, long-range information relay in an artificial molecular array assembled from modular DNA structural units. The dynamic DNA molecular array exhibits transformations with programmable initiation, propagation, and regulation. The transformation of the array can be initiated at selected units and then propagated, without addition of extra triggers, to neighboring units and eventually the entire array. The specific information pathways by which this transformation occurs can be controlled by altering the design of individual units and the arrays.

中文翻译:

信息中继驱动的DNA分子阵列重构

在 DNA 瓦片上传递信息 模块化 DNA 单元阵列可以通过改变其内部形状以响应 DNA 触发链的结合来传递信息。宋等人。合成了双链 DNA 的矩形阵列(参见 Yang 和 Lin 的观点)。通过夹住一对相对的顶点,瞬态正方形配置转变为两个稳定的矩形结构。DNA 触发链的结合导致转换为替代的稳定构型。因此,瓷砖会沿着特定路径创建级联变换,从而传输有关绑定发生位置的信息。科学,这个问题 p。eaan3377; 另见第。352 DNA 阵列的转化是由相互连接的分子单元之间的信息传播途径引导的。引言分子水平的信息传递是许多化学和生物过程中的基本现象。合成分子自组装的一个关键挑战是构建模拟可控系统中这些复杂动态行为的人工结构。一条有前途的路线是 DNA 自组装,这是一种设计和构建任意形状的人工纳米结构的有效方法,其复杂性和精度不断提高。尽管如此,尽管最近在构建可重构 DNA 纳米结构方面取得了进展,这些纳米结构会根据不同的物理或化学线索进行定制的组装后转换,但大规模复杂 DNA 结构的动态行为仍然有限。现有系统通常表现出相对简单的动态行为,涉及单个步骤或几个步骤的转换。此外,许多这些结构主要包含由一些小的可重构域连接的静态段。基本原理在这里,我们在由模块化 DNA 反连接单元组装的人工分子阵列中展示了规定的远程信息中继。小的动态反连接单元包含四个等长的 DNA 双螺旋结构域和四个动态切口点,并且可以通过中间开放构象在两个稳定构象之间切换。在阵列中,信息中继的驱动力是基数堆叠:一个反结单元的构象转换将导致变换单元与其相邻单元之间的界面变成具有弱碱基堆叠的高能构象,从而导致相邻单元发生变换。阵列转换相当于分子“多米诺阵列”:一旦在几个选定的单元上启动,转换就会传播到相邻单元,并最终传播到整个阵列,而无需添加额外的“触发链”。通过向特定单元添加触发链,或通过改变单个单元的设计、单元之间的连接和阵列的几何形状,可以控制发生这种转换的特定信息通路。结果 可重构 DNA 中继阵列是通过使用折纸和单链砖方法构建的。在一锅组装中,我们观察到由反结单元构建的阵列表现出一系列形状以适应反结构象的不同组合。通过结合固定链,我们可以将阵列锁定为规定的构象。添加的固定链越多,组装向相应阵列构象移动的幅度越大。其他因素,包括阵列的大小和纵横比、阵列的连接模式、阵列的 DNA 序列、阳离子浓度和温度,已被证明会影响一锅组装的结果。用预组装的阵列演示了转换级联。当从一种构象开始时,在阵列的选定位置添加触发链会引发从选定位点的结构转变,并以逐步方式传播到阵列的其余部分,而无需在其他位置添加额外的触发链。释放旧的触发链并添加新的触发链可以将阵列转换回其初始构象——一个可以重复多轮的可逆过程。此外,我们能够控制传播路径以遵循规定的路线,并通过机械解耦反结或引入“块链”来停止然后恢复传播。阵列转换的动力学可以通过升高的温度或甲酰胺来增强。这些组装和转化主要通过原子力显微镜和天然琼脂糖凝胶电泳进行研究。结论我们的工作证明了 DNA 纳米阵列的受控、多步、长程转换,由互连的模块化动态单元组装而成,可以将其结构信息传递给邻居。阵列的动态行为可以通过外部因素、阵列的形状和大小、选定单元的转换启动以及工程信息传播路径来调节。我们预计 DNA 中继阵列将为如何构建具有越来越大的尺寸和复杂动态行为的纳米结构提供新的思路,并可能实现一系列应用,例如构建分子装置以检测分子相互作用并将其转化为 DNA 的构象变化结构,以远程触发随后的分子事件。DNA“多米诺”纳米阵列中的信息中继。以类似于多米诺阵列(顶部)的方式,分子 DNA 纳米阵列在逐步中继过程中转化,由触发链与单个单元(中间)的杂交启动。AFM 证实了纳米阵列转化的不同阶段(底部)。比例尺,50 nm。分子水平的信息传递是许多化学和生物过程中的基本现象,例如复杂的信号级联。合成分子自组装的一个关键挑战是构建在可控系统中模仿这些复杂行为的人工结构。我们在由模块化 DNA 结构单元组装的人工分子阵列中展示了规定的远程信息中继。动态 DNA 分子阵列表现出具有可编程起始、传播和调节的转化。阵列的转换可以在选定的单元处启动,然后在不添加额外触发器的情况下传播到相邻单元并最终传播到整个阵列。可以通过改变单个单元和阵列的设计来控制发生这种转换的特定信息通路。
更新日期:2017-06-22
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