合成微生物群落中的多细胞反馈控制策略：从嵌入式到分布式控制
Multicellular Feedback Control Strategies in Synthetic Microbial Consortia: From Embedded to Distributed Control
AI总结：
本文探讨了合成微生物群落中多细胞反馈控制策略的设计与应用，强调分布式控制在提高系统鲁棒性和模块化重用方面的优势，并指出生物制造等实际应用中的关键挑战。
摘要：
生活在中的生物体依赖于内源性反馈机制来在不确定性和环境波动存在的情况下维持稳态。在控制系统工程和合成生物学交汇处出现的一个新兴挑战是设计可靠的反馈策略来调节细胞行为和集体生物功能。在本文中，我们回顾了多细胞反馈控制的最新进展，其中传感、计算和执行被分布到不同细胞群体中，从而形成由分子通信控制的生物多智能体控制系统。从控制论的角度来看，这些群落可以被解释为分布式生物分子控制系统，其中群体间的协调取代了嵌入式调节。我们调查了理论框架、控制架构和建模方法，从群体层面动态到空间意识的基于代理的模拟，讨论了在工程大肠杆菌群落中的实验演示。我们强调了将控制功能分布在群体中可以减少代谢负担、缓解回退性、提高对不确定性的鲁棒性，并使控制组件的模块化重用成为可能。除了调节基因表达外，我们还讨论了新兴的群体组成控制问题，其中协调生长和竞争细胞群体成为控制目标的重要组成部分。最后，我们概述了必须在多细胞控制策略应用于实际应用之前必须解决的关键挑战，如生物制造、环境修复和治疗系统。这些挑战涵盖了建模和仿真、实验平台开发、协调和组成控制以及长期进化稳定性。
英文摘要：
Living organisms rely on endogenous feedback mechanisms to maintain homeostasis in the presence of uncertainty and environmental fluctuations. An emerging challenge at the interface of control systems engineering and synthetic biology is the design of reliable feedback strategies to regulate cellular behavior and collective biological functions. In this article, we review recent advances in multicellular feedback control, where sensing, computation, and actuation are distributed across different cell populations within synthetic microbial consortia, giving rise to biological multiagent control systems governed by molecular communication. From a control-theoretic perspective, these consortia can be interpreted as distributed biomolecular control systems, where coordination among populations replace embedded regulation. We survey theoretical frameworks, control architectures, and modeling approaches, ranging from aggregate population-level dynamics to spatially aware agent-based simulations, and discuss experimental demonstrations in engineered \textit{Escherichia coli} consortia. We highlight how distributing control functions across populations can reduce metabolic burden, mitigate retroactivity, improve robustness to uncertainty, and enable modular reuse of control components. Beyond regulation of gene expression, we discuss the emerging problem of population composition control, where coordination among growing and competing cell populations becomes an integral part of the control objective. Finally, we outline key open challenges that must be addressed before multicellular control strategies can be deployed in real-world applications such as biomanufacturing, environmental remediation, and therapeutic systems. These challenges span modeling and simulation, experimental platform development, coordination and composition control, and long-term evolutionary stability.
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