Department of Mathematics, Imperial College London, London, United Kingdom.
MRC London Institute of Medical Sciences (LMS), London, United Kingdom.
PLoS Comput Biol. 2020 Sep 28;16(9):e1008245. doi: 10.1371/journal.pcbi.1008245. eCollection 2020 Sep.
Universal observations in Biology are sometimes described as "laws". In E. coli, experimental studies performed over the past six decades have revealed major growth laws relating ribosomal mass fraction and cell size to the growth rate. Because they formalize complex emerging principles in biology, growth laws have been instrumental in shaping our understanding of bacterial physiology. Here, we discovered a novel size law that connects cell size to the inverse of the metabolic proteome mass fraction and the active fraction of ribosomes. We used a simple whole-cell coarse-grained model of cell physiology that combines the proteome allocation theory and the structural model of cell division. This integrated model captures all available experimental data connecting the cell proteome composition, ribosome activity, division size and growth rate in response to nutrient quality, antibiotic treatment and increased protein burden. Finally, a stochastic extension of the model explains non-trivial correlations observed in single cell experiments including the adder principle. This work provides a simple and robust theoretical framework for studying the fundamental principles of cell size determination in unicellular organisms.
生物学中的普遍观察有时被描述为“定律”。在大肠杆菌中,过去六十年的实验研究揭示了与核糖体质量分数和细胞大小与生长速率相关的主要生长定律。由于它们使生物学中复杂的新兴原理形式化,生长定律在塑造我们对细菌生理学的理解方面发挥了重要作用。在这里,我们发现了一个新的大小定律,将细胞大小与代谢蛋白质组质量分数的倒数和核糖体的活性部分联系起来。我们使用了一种简单的细胞生理学整体粗粒模型,该模型结合了蛋白质组分配理论和细胞分裂的结构模型。这个综合模型捕获了所有可用的实验数据,这些数据将细胞蛋白质组组成、核糖体活性、分裂大小和生长速率与营养质量、抗生素处理和增加的蛋白质负担联系起来。最后,模型的随机扩展解释了在单细胞实验中观察到的非平凡相关性,包括加法器原理。这项工作为研究单细胞生物中细胞大小决定的基本原理提供了一个简单而强大的理论框架。