Nano: Error-Resilient DNA Tiling Assemblies

自下而上构建纳米结构的自组装过程对新兴的纳米科学学科具有基础性的重要性。例如，DNA瓷砖纳米结构自组装成2D晶格可以用来从更小的单位纳米结构制造图案化的纳米结构，DNA瓷砖是被称为DNA瓷砖的组件，其他分子如金属粒子和蛋白质可以附着在DNA瓷砖上，DNA瓷砖晶格可以用于并行通用计算。然而，分子尺度上的自组装容易出现相当高的错误率，大约在0.5%到5%之间，而大规模实验实现DNA拼接的关键障碍是自组装过程中的显著错误率。平铺误差问题对于使用计算平铺来产生复杂图案的DNA晶格来说尤其关键，限制和/或消除自组装中的这些错误可能是纳米结构自组装面临的最重要的一个主要挑战。提出的研究目标是开发容错自组装方法；通过概率分析、动力学分析和计算机模拟对这些方法进行分析；并通过一系列实验室实验来验证这些容错自组装方法。研究将在DNA拼接组件的背景下进行。Winfree的前期工作提供了一种方法，可以在不降低组装单个瓷砖的固有错误率的情况下减少瓷砖自组装错误，然而，这种技术导致了最终组装结构的大小是原始结构的四倍。杜克大学的这个研究小组已经开发出紧凑型抗恐怖瓷砖方法，这种方法不会增加瓷砖组合的大小。他们将测试他们的新的具有容错能力的瓷砖方法，这种方法使用覆盖冗余，使得瓷砖与其相邻瓷砖之间的单个衬垫不匹配会导致该瓷砖相邻瓷砖之间的一个或多个进一步衬垫不匹配。这项研究将采用理论和实验相结合的方法。首先将使用理论概率动力学分析和计算机模拟拼接的经验研究来验证这些容错覆盖冗余拼接方法；该分析将允许预测降低的错误率，并验证装配速度没有降低。在此之后，将使用DNA瓷砖进行实际实验演示，总体目标是演示数千块瓷砖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.