Institute of Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
Theoretical Physical Chemistry, Research Unit Molecular Systems, University of Liege, 4000 Liege, Belgium.
Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2843-2848. doi: 10.1073/pnas.1816670116. Epub 2019 Feb 6.
Cellular transformations are driven by environmentally triggered complex dynamic networks, which include signal-triggered feedback processes, cascaded reactions, and switchable transformations. We apply the structural and functional information encoded in the sequences of nucleic acids to construct signal-triggered constitutional dynamic networks (CDNs) that mimic the functions of natural networks. Using predesigned hairpin structures as triggers, the network generates functional strands, which stabilize one or the other of the constituents of the network, leading to feedback-driven reconfiguration and time-dependent equilibration of the networks. Using structurally designed hairpins, positive-feedback or negative-feedback mechanisms operated by the CDNs are demonstrated. With two predesigned hairpins, the coupled consecutive operations of negative/positive- or positive/positive- feedback cascades are accomplished. The time-dependent composition changes of the networks are well reproduced by chemical kinetics simulations that provide predictive behaviors of the network, under variable auxiliary conditions. Beyond mimicking natural network properties and functions by means of the synthetic nucleic-acid-based CDNs, the systems introduce versatile perspectives for the design of amplified sensors (sensing of miRNA-376a) and the development of logic gate circuits.
细胞转化是由环境触发的复杂动态网络驱动的，这些网络包括信号触发的反馈过程、级联反应和可切换的转化。我们应用核酸序列中编码的结构和功能信息来构建模拟自然网络功能的信号触发结构动态网络（CDN）。使用预先设计的发夹结构作为触发物，该网络产生功能性链，稳定网络的一个或另一个组成部分，导致反馈驱动的网络重新配置和随时间的平衡。使用结构设计的发夹，CDN 操作的正反馈或负反馈机制得到了证明。使用两个预先设计的发夹，完成了负/正-或正/正-反馈级联的连续耦合操作。通过化学动力学模拟很好地再现了网络的时变组成变化，该模拟提供了在辅助条件变化下网络的预测行为。除了通过基于合成核酸的 CDN 模拟自然网络的特性和功能外，该系统还为设计放大传感器（miRNA-376a 的传感）和开发逻辑门电路引入了多种视角。
