Menon Govind, Okeke Chinedu, Krishnan J
Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, London, SW7 2AZ, UK.
Institute for Systems and Synthetic Biology, Imperial College London, London, SW7 2AZ, UK.
Sci Rep. 2017 Sep 21;7(1):12057. doi: 10.1038/s41598-017-11081-8.
Compartmentalization is a fundamental ingredient, central to the functioning of biological systems at multiple levels. At the cellular level, compartmentalization is a key aspect of the functioning of biochemical pathways and an important element used in evolution. It is also being exploited in multiple contexts in synthetic biology. Accurate understanding of the role of compartments and designing compartmentalized systems needs reliable modelling/systems frameworks. We examine a series of building blocks of signalling and metabolic pathways with compartmental organization. We systematically analyze when compartmental ODE models can be used in these contexts, by comparing these models with detailed reaction-transport models, and establishing a correspondence between the two. We build on this to examine additional complexities associated with these pathways, and also examine sample problems in the engineering of these pathways. Our results indicate under which conditions compartmental models can and cannot be used, why this is the case, and what augmentations are needed to make them reliable and predictive. We also uncover other hidden consequences of employing compartmental models in these contexts. Or results contribute a number of insights relevant to the modelling, elucidation, and engineering of biochemical pathways with compartmentalization, at the core of systems and synthetic biology.
区室化是一个基本要素，对于多层次生物系统的运作至关重要。在细胞层面，区室化是生化途径运作的关键方面，也是进化过程中使用的一个重要元素。它在合成生物学的多种情境中也得到了应用。准确理解区室的作用并设计区室化系统需要可靠的建模/系统框架。我们研究了一系列具有区室组织的信号传导和代谢途径的构建模块。通过将这些模型与详细的反应-传输模型进行比较，并在两者之间建立对应关系，我们系统地分析了何时可以在这些情境中使用区室常微分方程模型。在此基础上，我们研究了与这些途径相关的其他复杂性，还研究了这些途径工程中的示例问题。我们的结果表明了在哪些条件下可以使用和不能使用区室模型，为什么会这样，以及需要进行哪些扩充才能使它们可靠且具有预测性。我们还揭示了在这些情境中使用区室模型的其他潜在后果。我们的结果为系统生物学和合成生物学核心的具有区室化的生化途径的建模、阐释和工程提供了许多相关见解。
