Discretised flux balance analysis for reaction-diffusion simulation of single-cell metabolism
Discretised flux balance analysis for reaction-diffusion simulation of single-cell metabolism
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DOI：
10.1101/2023.08.01.551453
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发表时间：
2024-01
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影响因子：
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通讯作者：
Yin Hoon Chew;F. Spill
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文献类型：
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作者：
Yin Hoon Chew;F. Spill
代谢物必须在它们占据的亚细胞区室中扩散到酶所在的特定位置，因此可能会发生反应。传统的通量平衡分析 (FBA) 是一种基于线性规划的方法，通常用于模拟代谢，隐含地假设所有酶反应都不是扩散限制的，尽管情况可能并非总是如此。在这项工作中，我们开发了一种在基于网格的系统上实施 FBA 的空间方法，以便能够探索扩散对新陈代谢的影响。具体来说，该方法将活细胞离散成二维网格，表示每个网格元素中的代谢反应以及代谢物在相邻元素之间的扩散，并将系统模拟为单个线性规划问题。我们改变网格中的行数和列数来模拟不同的细胞形状，并且该方法能够捕捉不同形状的扩散效应。然后，我们使用该方法来模拟异质酶分布，这表明对群体水平变异性的理论影响。我们建议使用这种方法及其未来的扩展来探索亚细胞区室及其分子的时空组织如何影响细胞行为。
Metabolites have to diffuse within the sub-cellular compartments they occupy to specific locations where enzymes are, so reactions could occur. Conventional flux balance analysis (FBA), a method based on linear programming that is commonly used to model metabolism, implicitly assumes that all enzymatic reactions are not diffusion-limited though that may not always be the case. In this work, we have developed a spatial method that implements FBA on a grid-based system, to enable the exploration of diffusion effects on metabolism. Specifically, the method discretises a living cell into a two-dimensional grid, represents the metabolic reactions in each grid element as well as the diffusion of metabolites to and from neighbouring elements, and simulates the system as a single linear programming problem. We varied the number of rows and columns in the grid to simulate different cell shapes, and the method was able to capture diffusion effects at different shapes. We then used the method to simulate heterogeneous enzyme distribution, which suggested a theoretical effect on variability at the population level. We propose the use of this method, and its future extensions, to explore how spatiotemporal organisation of sub-cellular compartments and the molecules within could affect cell behaviour.