Layered feedback is an optimization strategy in feedback control designs widely used in electrical and mechanical engineering. Layered control theory suggests that the performance of controllers is bound by the universal robustness-efficiency tradeoff limit, which could be overcome by layering two or more feedbacks together. In natural biological networks, genes are often regulated with redundancy and layering to adapt to environmental perturbations. Control theory hypothesizes that this layering architecture is also adopted by nature to overcome this performance trade-off. In this work, we validated this property of layered control with a synthetic network in living E. coli cells. We performed system analysis on a node-based design to confirm the tradeoff properties before proceeding to simulations with an effective mechanistic model, which guided us to the best performing design to engineer in cells. Finally, we interrogated its system dynamics experimentally with eight sets of perturbations on chemical signals, nutrient abundance, and growth temperature. For all cases, we consistently observed that the layered control overcomes the robustness-efficiency trade-off limit. This work experimentally confirmed that layered control could be adopted in synthetic biomolecular networks as a performance optimization strategy. It also provided insights in understanding genetic feedback control architectures in nature.

中文翻译：

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分层反馈控制克服了合成生物分子网络中的性能权衡

分层反馈是广泛应用于电气和机械工程的反馈控制设计中的一种优化策略。分层控制理论表明，控制器的性能受通用鲁棒性-效率权衡限制的约束，这可以通过将两个或多个反馈分层在一起来克服。在自然生物网络中，基因通常通过冗余和分层进行调节以适应环境扰动。控制理论假设自然也采用这种分层架构来克服这种性能权衡。在这项工作中，我们通过活大肠杆菌中的合成网络验证了分层控制的这种特性细胞。我们对基于节点的设计进行了系统分析，以确认权衡特性，然后再使用有效的机械模型进行仿真，这引导我们进行最佳性能设计以进行单元工程。最后，我们通过八组化学信号、营养丰度和生长温度的扰动，通过实验询问了它的系统动力学。对于所有情况，我们一致观察到分层控制克服了稳健性-效率权衡限制。这项工作通过实验证实，可以在合成生物分子网络中采用分层控制作为性能优化策略。它还提供了理解自然界中遗传反馈控制架构的见解。