Department of Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, CA, USA.
Department of Chemical Science and Technologies, University of Rome, Tor Vergata, Via della Ricerca Scientifica, Rome, Italy.
Nat Commun. 2024 Oct 3;15(1):8561. doi: 10.1038/s41467-024-52986-z.
Living cells regulate the dynamics of developmental events through interconnected signaling systems that activate and deactivate inert precursors. This suggests that similarly, synthetic biomaterials could be designed to develop over time by using chemical reaction networks to regulate the availability of assembling components. Here we demonstrate how the sequential activation or deactivation of distinct DNA building blocks can be modularly coordinated to form distinct populations of self-assembling polymers using a transcriptional signaling cascade of synthetic genes. Our building blocks are DNA tiles that polymerize into nanotubes, and whose assembly can be controlled by RNA molecules produced by synthetic genes that target the tile interaction domains. To achieve different RNA production rates, we use a strategy based on promoter "nicking" and strand displacement. By changing the way the genes are cascaded and the RNA levels, we demonstrate that we can obtain spatially and temporally different outcomes in nanotube assembly, including random DNA polymers, block polymers, and as well as distinct autonomous formation and dissolution of distinct polymer populations. Our work demonstrates a way to construct autonomous supramolecular materials whose properties depend on the timing of molecular instructions for self-assembly, and can be immediately extended to a variety of other nucleic acid circuits and assemblies.
活细胞通过相互连接的信号系统来调节发育事件的动态，这些信号系统激活和失活惰性前体。这表明，类似地，合成生物材料可以通过使用化学反应网络来调节组装成分的可用性来设计为随时间发展。在这里，我们展示了如何使用合成基因的转录信号级联，通过模块化协调不同 DNA 构建块的顺序激活或失活，从而形成具有不同自组装聚合物的不同群体。我们的构建块是聚合形成纳米管的 DNA 瓦片，其组装可以通过针对瓦片相互作用域的合成基因产生的 RNA 分子来控制。为了获得不同的 RNA 产生率，我们使用了一种基于启动子“缺口”和链置换的策略。通过改变基因级联和 RNA 水平的方式，我们证明我们可以在纳米管组装中获得空间和时间上不同的结果，包括随机 DNA 聚合物、嵌段聚合物，以及不同聚合物群体的自主形成和溶解。我们的工作展示了一种构建自主超分子材料的方法，其性质取决于自组装的分子指令的时间，并可以立即扩展到各种其他核酸电路和组装。
