Effective design principles for leakless strand displacement systems
Effective design principles for leakless strand displacement systems
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DOI：
10.1073/pnas.1806859115
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发表时间：
2018-12-26
影响因子：
11.1
通讯作者：
Soloveichik, David
中科院分区：
文献类型：
--
作者：
Wang, Boya;Thachuk, Chris;Soloveichik, David
具有可编程行为的人工设计的分子系统已成为化学，生物学，材料科学和医学方面的宝贵工具。尽管生物调节途径中的信息处理对于误差非常健壮，但对于类似鲁棒的设计分子系统仍然是一个挑战。通过完全由DNA的二级结构确定的功能，链位移已成为用于无细胞生化网络的独特用途构建块。在这里，我们通过实验研究了一个设计原理，以减少在没有输入的情况下（泄漏），这是一种严重降低灵敏度并破坏链位移级联反应的侧反应。受到电气工程中利用冗余的错误校正方法的启发，我们确保通过逻辑冗余泄漏更高的能量罚款。原则上，我们的设计策略能够将泄漏降低到任意较低的水平，并且我们通过实验测试了将一个序列转换为另一个序列的核心“翻译器”组件的两个级别的泄漏降低。我们表明，即使是高达典型的100倍的浓度，泄漏也无法测量。除了单个翻译器之外，我们还构建了一个由9条链位移步骤的快速和低螺旋转换器级联，由10个翻译器组成，这表明我们的设计原理可用于有效地减少更复杂的化学系统中的泄漏。
Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades. Inspired by error correction methods exploiting redundancy in electrical engineering, we ensure a higher-energy penalty to leak via logical redundancy. Our design strategy is, in principle, capable of reducing leak to arbitrarily low levels, and we experimentally test two levels of leak reduction for a core "translator" component that converts a signal of one sequence into that of another. We show that the leak was not measurable in the high-redundancy scheme, even for concentrations that are up to 100 times larger than typical. Beyond a single translator, we constructed a fast and low-leak translator cascade of nine strand displacement steps and a logic OR gate circuit consisting of 10 translators, showing that our design principle can be used to effectively reduce leak in more complex chemical systems.