4-bit adhesion logic enables universal multicellular interface patterning.

4-bit adhesion logic enables universal multicellular interface patterning.
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DOI:
10.1038/s41586-022-04944-2
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发表时间:
2022-08
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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多细胞系统,从细菌生物膜到人体器官,在不同的细胞群之间形成界面(或边界),以在空间上组织多种功能。具有足够描述性的遗传工具的进化可能引发了复杂的多细胞生命和模式的爆发。合成生物学旨在为实际应用设计多细胞系统,并作为自然系统的一种构建理解方法。然而,我们设计多细胞界面模式的能力仍然非常有限,因为合成细胞-细胞粘附工具包和合适的模式算法还不发达。在此,我们引入了一种具有群菌的合成细胞-细胞粘附素逻辑,并建立了多细胞界面模式的精确工程、预测建模和算法编程。我们展示了通过蜂群粘附机制、对界面几何形状的定量控制以及发育组织者和形态原场的粘附介导的类似物来产生界面。使用平铺和四色映射概念,我们确定了创建通用目标图案的算法。这种合成的4位粘附逻辑推进了实际应用,如人类可读的分子诊断,生物表面的空间流体控制和可编程的自生长材料。值得注意的是,仅仅四个粘附素的最小集合代表4位信息,足以编程通用镶嵌模式,这意味着复杂多细胞系统的进化和工程的低临界阈值。介绍了一种使用4位信息的蜂群大肠杆菌的合成细胞-细胞粘附逻辑,使接口编程能够在大范围内组合形成通用镶嵌图案。
Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems. However, our ability to engineer multicellular interface patterns is still very limited, as synthetic cell–cell adhesion toolkits and suitable patterning algorithms are underdeveloped. Here we introduce a synthetic cell–cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems. A synthetic cell-cell adhesion logic using swarming E. coli with 4 bits of information is introduced, enabling the programming of interfaces that combine to form universal tessellation patterns over a large scale.
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