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Dynamic Reconfiguration of Subcompartment Architectures in Artificial Cells
ACS Nano ( IF 17.1 ) Pub Date : 2022-06-13 , DOI: 10.1021/acsnano.2c02195
Greta Zubaite 1, 2 , James W Hindley 1, 3, 4 , Oscar Ces 1, 3, 4 , Yuval Elani 2, 4
Affiliation  

Artificial cells are minimal structures constructed from biomolecular building blocks designed to mimic cellular processes, behaviors, and architectures. One near-ubiquitous feature of cellular life is the spatial organization of internal content. We know from biology that organization of content (including in membrane-bound organelles) is linked to cellular functions and that this feature is dynamic: the presence, location, and degree of compartmentalization changes over time. Vesicle-based artificial cells, however, are not currently able to mimic this fundamental cellular property. Here, we describe an artificial cell design strategy that addresses this technological bottleneck. We create a series of artificial cell architectures which possess multicompartment assemblies localized either on the inner or on the outer surface of the artificial cell membrane. Exploiting liquid–liquid phase separation, we can also engineer spatially segregated regions of condensed subcompartments attached to the cell surface, aligning with coexisting membrane domains. These structures can sense changes in environmental conditions and respond by reversibly transitioning from condensed multicompartment layers on the membrane surface to a dispersed state in the cell lumen, mimicking the dynamic compartmentalization found in biological cells. Likewise, we engineer exosome-like subcompartments that can be released to the environment. We can achieve this by using two types of triggers: chemical (addition of salts) and mechanical (by pulling membrane tethers using optical traps). These approaches allow us to control the compartmentalization state of artificial cells on population and single-cell levels.

中文翻译:

人工细胞中子隔间结构的动态重构

人造细胞是由旨在模拟细胞过程、行为和结构的生物分子构建块构建的最小结构。细胞生命的一个几乎无处不在的特征是内部内容的空间组织。我们从生物学中知道内容的组织(包括在膜结合细胞器中)与细胞功能有关,并且该特征是动态的:区室化的存在、位置和程度随时间而变化。然而,基于囊泡的人造细胞目前无法模仿这种基本的细胞特性。在这里,我们描述了一种解决这一技术瓶颈的人工细胞设计策略。我们创建了一系列人造细胞结构,这些结构具有位于人造细胞膜内表面或外表面的多隔室组件。利用液-液相分离,我们还可以设计附着在细胞表面的浓缩亚室的空间隔离区域,与共存的膜域对齐。这些结构可以感知环境条件的变化,并通过从膜表面上的浓缩多隔室层可逆地转变为细胞腔中的分散状态来做出响应,模仿生物细胞中发现的动态区室化。同样,我们设计了可以释放到环境中的类外泌体亚区室。我们可以通过使用两种类型的触发器来实现这一点:化学(添加盐)和机械(通过使用光阱拉动膜系绳)。这些方法使我们能够在群体和单细胞水平上控制人工细胞的区室化状态。
更新日期:2022-06-13
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