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通过体外相互连接的合成基因网络对多组分聚合物系统进行发育组装。

Developmental assembly of multi-component polymer systems through interconnected synthetic gene networks in vitro.

机构信息

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.

出版信息

Nat Commun. 2024 Oct 3;15(1):8561. doi: 10.1038/s41467-024-52986-z.


DOI:10.1038/s41467-024-52986-z
PMID:39362892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11452209/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/3ba6b44ad2b5/41467_2024_52986_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/78ef7d5eb812/41467_2024_52986_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/87cf2386e6f7/41467_2024_52986_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/dba200775b64/41467_2024_52986_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/5f201999587c/41467_2024_52986_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/273101c89934/41467_2024_52986_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/3ba6b44ad2b5/41467_2024_52986_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/78ef7d5eb812/41467_2024_52986_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/87cf2386e6f7/41467_2024_52986_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/dba200775b64/41467_2024_52986_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/5f201999587c/41467_2024_52986_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/273101c89934/41467_2024_52986_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/11452209/3ba6b44ad2b5/41467_2024_52986_Fig6_HTML.jpg

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[4]
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[7]
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[8]
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[9]
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引用本文的文献

[1]
Microswimmers That Flex: Advancing Microswimmers with Templated Assembly and Responsive DNA Nanostructures.

Acc Mater Res. 2025-7-14

本文引用的文献

[1]
DNA-Based Signaling Networks for Transient Colloidal Co-Assemblies.

J Am Chem Soc. 2023-8-16

[2]
DNA-Origami Line-Actants Control Domain Organization and Fission in Synthetic Membranes.

J Am Chem Soc. 2023-5-24

[3]
Dynamic Reconfigurable DNA Nanostructures, Networks and Materials.

Angew Chem Int Ed Engl. 2023-4-24

[4]
Standardized excitable elements for scalable engineering of far-from-equilibrium chemical networks.

Nat Chem. 2022-11

[5]
A DNA origami rotary ratchet motor.

Nature. 2022-7

[6]
Signal-processing and adaptive prototissue formation in metabolic DNA protocells.

Nat Commun. 2022-7-8

[7]
Dissipative DNA nanotechnology.

Nat Chem. 2022-6

[8]
Protocellular CRISPR/Cas-Based Diffusive Communication Using Transcriptional RNA Signaling.

Angew Chem Int Ed Engl. 2022-6-27

[9]
Automated Design of Robust Genetic Circuits: Structural Variants and Parameter Uncertainty.

ACS Synth Biol. 2021-12-17

[10]
DNA Origami Meets Bottom-Up Nanopatterning.

ACS Nano. 2021-7-27

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