Tran Nguyen Hoai Nam, Nguyen An, Rahman Tasfia Wasima, Baetica Ania-Ariadna
Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, Pennsylvania 19104, United States.
School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, United States.
ACS Synth Biol. 2025 Apr 18;14(4):1099-1111. doi: 10.1021/acssynbio.4c00704. Epub 2025 Apr 8.
Natural biological systems use feedback regulation to effectively respond and adapt to their changing environment. Even though in engineered systems we understand how accurate feedback can be depending on the electronic or mechanical parts that it is implemented with, we largely lack a similar theoretical framework to study feedback regulation in biological systems. Specifically, it is not fully understood or quantified how accurate or robust the implementation of biological feedback actually is. In this paper, we study the sensitivity of biological feedback to variations in biochemical parameters using five example circuits: positive autoregulation, negative autoregulation, double-positive feedback, positive-negative feedback, and double-negative feedback (the toggle switch). We find that some of these examples of biological feedback are subjected to fundamental performance trade-offs, and we propose multi-objective optimization as a framework to study their properties. The impact of this work is to improve robust circuit design for synthetic biology and to improve our understanding of feedback for systems biology.
自然生物系统利用反馈调节来有效地响应和适应不断变化的环境。尽管在工程系统中，我们了解取决于所使用的电子或机械部件，反馈可以有多精确，但在很大程度上，我们缺乏一个类似的理论框架来研究生物系统中的反馈调节。具体而言，生物反馈的实际实施有多精确或稳健，尚未得到充分理解或量化。在本文中，我们使用五个示例电路研究生物反馈对生化参数变化的敏感性：正自调节、负自调节、双正反馈、正负反馈和双负反馈（触发开关）。我们发现，这些生物反馈示例中的一些存在基本的性能权衡，我们提出多目标优化作为研究其特性的框架。这项工作的影响在于改进合成生物学的稳健电路设计，并增进我们对系统生物学反馈的理解。
