利用简单的 DNA 构建模块来创建复杂的原细胞和原组织。

Creating complex protocells and prototissues using simple DNA building blocks.

机构信息

Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, WC1E 6BT, UK.

Department of Chemistry, Institute of Structural and Molecular Biology, University Collegfige London, London, WC1H 0AJ, UK.

出版信息

Nat Commun. 2023 Mar 10;14(1):1314. doi: 10.1038/s41467-023-36875-5.

Abstract

Building synthetic protocells and prototissues hinges on the formation of biomimetic skeletal frameworks. Recreating the complexity of cytoskeletal and exoskeletal fibers, with their widely varying dimensions, cellular locations and functions, represents a major material hurdle and intellectual challenge which is compounded by the additional demand of using simple building blocks to ease fabrication and control. Here we harness simplicity to create complexity by assembling structural frameworks from subunits that can support membrane-based protocells and prototissues. We show that five oligonucleotides can anneal into nanotubes or fibers whose tunable thicknesses and lengths spans four orders of magnitude. We demonstrate that the assemblies' location inside protocells is controllable to enhance their mechanical, functional and osmolar stability. Furthermore, the macrostructures can coat the outside of protocells to mimic exoskeletons and support the formation of millimeter-scale prototissues. Our strategy could be exploited in the bottom-up design of synthetic cells and tissues, to the generation of smart material devices in medicine.

摘要

构建合成原细胞和原组织依赖于仿生骨架的形成。重现细胞骨架和外骨骼纤维的复杂性,包括它们广泛变化的尺寸、细胞位置和功能,是一个主要的材料障碍和知识挑战,而使用简单的构建块来简化制造和控制则增加了更多的需求。在这里,我们通过从能够支持基于膜的原细胞和原组织的亚单位组装结构框架,利用简单来创造复杂。我们表明,五个寡核苷酸可以退火成纳米管或纤维,其可调厚度和长度跨越四个数量级。我们证明了组装体在原细胞内的位置是可控的,以增强其机械、功能和渗透压稳定性。此外,这些宏观结构可以涂覆在原细胞的外部,以模拟外骨骼并支持毫米级原组织的形成。我们的策略可以用于合成细胞和组织的自下而上设计,以及在医学中制造智能材料设备。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b3/10006096/50fedf2cc84e/41467_2023_36875_Fig1_HTML.jpg

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