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4-bit adhesion logic enables universal multicellular interface patterning
Nature ( IF 64.8 ) Pub Date : 2022-08-10 , DOI: 10.1038/s41586-022-04944-2
Honesty Kim 1 , Dominic J Skinner 2 , David S Glass 3 , Alexander E Hamby 1 , Bradey A R Stuart 1 , Jörn Dunkel 2 , Ingmar H Riedel-Kruse 1, 4, 5
Affiliation  

Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions1,2. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning3,4. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems5,6,7,8. However, our ability to engineer multicellular interface patterns2,9 is still very limited, as synthetic cell–cell adhesion toolkits and suitable patterning algorithms are underdeveloped5,7,10,11,12,13. 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 materials5,6,7,8,14. 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 systems3,5.



中文翻译:

4 位粘附逻辑可实现通用多细胞界面图案化

从细菌生物膜到人体器官,多细胞系统在不同细胞群体之间形成界面(或边界),以在空间上组织多种功能1,2。充分描述性遗传工具包的进化可能引发了复杂的多细胞生命和模式的爆发3,4。合成生物学旨在设计用于实际应用的多细胞系统,并作为自然系统的构建理解方法5,6,7,8。然而,我们设计多细胞界面模式的能力2,9仍然非常有限,因为合成的细胞-细胞粘附工具包和合适的模式算法尚未开发5,7,10,11,12,13。在这里,我们引入了一种具有群聚细菌的合成细胞-细胞粘附素逻辑,并建立了多细胞界面模式的精确工程、预测模型和算法编程。我们通过集群粘附机制、对界面几何形状的定量控制以及发育组织者和形态发生素场的粘附介导的类似物来演示界面生成。使用平铺和四色映射概念,我们确定了用于创建通用目标模式的算法。这种合成的 4 位粘附逻辑推进了实际应用,例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自生长材料5,6,7,8,14。值得注意的是,仅四个粘附素的最小集合代表足以对通用镶嵌图案进行编程的 4 位信息,这意味着复杂多细胞系统的进化和工程的临界阈值较低3,5

更新日期:2022-08-11
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