Nano: Error-Resilient DNA Tiling Assemblies

自下而上构建纳米结构的自组装过程对纳米科学这一新兴学科具有重要意义。例如，DNA瓦片纳米结构自组装成2D晶格可以用于从称为DNA瓦片的较小单元纳米结构组件制造图案化的纳米结构，其他分子如金属颗粒和蛋白质可以附着在DNA瓦片上，并且DNA瓦片晶格可以用于执行并行通用计算。然而，在分子尺度上的自组装很容易出现相当高的错误率，范围从0.5%到5%之间，而大规模实验实施DNA拼接的关键障碍是自组装过程中的显著错误率。拼接误差的问题对于使用计算拼接来产生复杂图案的DNA晶格来说是特别关键的。限制和/或消除自组装中的这些误差可能是纳米结构自组装的唯一最重要的主要挑战。本研究的目标是开发容错自组装的方法;通过概率、动力学分析和计算机模拟来分析这些方法;并通过一系列实验室实验来证明这些容错自组装方法。研究将在DNA平铺组装的背景下进行。Winfree的先前工作提供了一种方法来减少拼接自组装错误，而不会降低组装单个瓷砖的固有错误率，然而，他的技术导致最终组装的结构是原始结构的四倍。杜克大学的这个研究小组已经开发出了一种不增加拼接组件大小的抗干扰拼接方法。他们将测试他们新的抗干扰拼接方法，该方法使用覆盖冗余，使得一个拼接块与其紧邻拼接块之间的单个焊盘不匹配迫使该拼接块附近的相邻拼接块之间出现一个或多个焊盘不匹配。本研究将采用理论与实验相结合的方法.理论概率动力学分析和实证研究的计算机模拟的平铺将首先被用来验证这些错误-消除overlay冗余平铺方法，分析将允许减少错误率的预测和验证的装配速度没有降低。在此之后，将使用DNA瓦片进行实际的实验演示，总体目标是证明数千个瓦片的无错误组装的可行性。

The self-assembly process for bottom-up construction of nanostructures is offundamental importance to the emerging discipline of Nanoscience. For example,the self-assembly of DNA tile nanostructures into 2D lattices can be used tomanufacture patterned nanostructures from smaller unit nanostructurescomponents known as DNA tiles on which other molecules such as metallicparticles and proteins can be affixed, and DNA tiling lattices can be used toperform parallel universal computation. However, self-assemblies at themolecular scale are prone to a quite high rate of error, ranging fromapproximately between 0.5% to 5%, and the key barrier to large-scaleexperimental implementation of DNA tiling is this significant error rate in the self-assemblyprocess. The problem of tiling errors is particularly critical for DNAlattices that use computational tilings to produce complex patterns, The limitationand/or elimination of these errors in self-assembly is perhaps the single mostimportant major challenge to nanostructure self-assembly. The goals of theproposed research are to develop methods for error-resilient self-assembly; toanalyze these by probabilistic, kinetic analysis and computer simulation; and todemonstrate these error-resilient self-assembly methods by a series of laboratoryexperiments. Research will be done in the context of DNA tiling assemblies. Priorwork by Winfree provided a method to decrease tiling self-assembly errorswithout decreasing the intrinsic error rate of assembling a single tile, however, histechnique resulted in a final assembled structure that is four times the size of theoriginal one. This research team at Duke University has developed compacterror-resilient tiling methods that do not increase the size of the tiling assembly.They will test their new error-resilient tiling methods that use overlay redundancysuch that a single pad mismatch between a tile and its immediate neighbor forcesone or more further pad mismatches between adjacent tiles in the neighborhoodof this tile. The research will use a combination of theoretical and experimentalmethods. Theoretical probabilistic kinetic analysis and empirical studies of thecomputer simulation of tilings will first be used to validate these error-resilientoverlay redundancy tiling methods; the analysis will allow prediction of thereduced error rate and verify the speed of the assembly is not reduced. Followingthis, actual experimental demonstrations will be made using DNA tiles, Theoverall goal is to demonstrate the feasibility of error-free assemblies of thousandsof tiles.