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芯片上人工细胞耦合遗传振荡器的同步和模式形成。

Synchrony and pattern formation of coupled genetic oscillators on a chip of artificial cells.

机构信息

Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, Israel, 76100.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel, 76100.

出版信息

Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):11609-11614. doi: 10.1073/pnas.1710620114. Epub 2017 Oct 16.

Abstract

Understanding how biochemical networks lead to large-scale nonequilibrium self-organization and pattern formation in life is a major challenge, with important implications for the design of programmable synthetic systems. Here, we assembled cell-free genetic oscillators in a spatially distributed system of on-chip DNA compartments as artificial cells, and measured reaction-diffusion dynamics at the single-cell level up to the multicell scale. Using a cell-free gene network we programmed molecular interactions that control the frequency of oscillations, population variability, and dynamical stability. We observed frequency entrainment, synchronized oscillatory reactions and pattern formation in space, as manifestation of collective behavior. The transition to synchrony occurs as the local coupling between compartments strengthens. Spatiotemporal oscillations are induced either by a concentration gradient of a diffusible signal, or by spontaneous symmetry breaking close to a transition from oscillatory to nonoscillatory dynamics. This work offers design principles for programmable biochemical reactions with potential applications to autonomous sensing, distributed computing, and biomedical diagnostics.

摘要

理解生化网络如何导致生命中大规模的非平衡自组织和模式形成是一个重大挑战,对可编程合成系统的设计具有重要意义。在这里,我们将无细胞遗传振荡器组装在芯片 DNA 隔室的空间分布系统中作为人工细胞,并在单细胞水平到多细胞尺度上测量反应-扩散动力学。使用无细胞基因网络,我们编程了控制振荡频率、种群变异性和动力学稳定性的分子相互作用。我们观察到频率同步、空间中同步的振荡反应和模式形成,这是集体行为的表现。随着隔室之间局部耦合的增强,同步发生。时空振荡要么是由可扩散信号的浓度梯度引起的,要么是由接近从振荡到非振荡动力学的转变的自发对称破缺引起的。这项工作为具有自主感应、分布式计算和生物医学诊断应用潜力的可编程生化反应提供了设计原则。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d37/5676917/6f6d6e94424b/pnas.1710620114fig01.jpg

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