Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS Comput Biol. 2022 Feb 18;18(2):e1009400. doi: 10.1371/journal.pcbi.1009400. eCollection 2022 Feb.
In eukaryotes, the cell volume is observed to be strongly correlated with the nuclear volume. The slope of this correlation depends on the cell type, growth condition, and the physical environment of the cell. We develop a computational model of cell growth and proteome increase, incorporating the kinetics of amino acid import, protein/ribosome synthesis and degradation, and active transport of proteins between the cytoplasm and the nucleoplasm. We also include a simple model of ribosome biogenesis and assembly. Results show that the cell volume is tightly correlated with the nuclear volume, and the cytoplasm-nucleoplasm transport rates strongly influence the cell growth rate as well as the cell/nucleus volume ratio (C/N ratio). Ribosome assembly and the ratio of ribosomal proteins to mature ribosomes also influence the cell volume and the cell growth rate. We find that in order to regulate the cell growth rate and the cell/nucleus volume ratio, the cell must optimally control groups of kinetic and transport parameters together, which could explain the quantitative roles of canonical growth pathways. Finally, although not explicitly demonstrated in this work, we point out that it is possible to construct a detailed proteome distribution using our model and RNAseq data, provided that a quantitative cell division mechanism is known.
在真核生物中,细胞体积与核体积密切相关。这种相关性的斜率取决于细胞类型、生长条件和细胞的物理环境。我们开发了一种细胞生长和蛋白质组增加的计算模型,其中包括氨基酸输入、蛋白质/核糖体合成和降解以及蛋白质在细胞质和核质之间的主动运输的动力学。我们还包括一个简单的核糖体生物发生和组装模型。结果表明,细胞体积与核体积密切相关,细胞质-核质运输速率强烈影响细胞生长速率以及细胞/核体积比(C/N 比)。核糖体组装和核糖体蛋白与成熟核糖体的比例也会影响细胞体积和细胞生长速率。我们发现,为了调节细胞生长速率和细胞/核体积比,细胞必须最佳地共同控制一组动力学和运输参数,这可以解释规范生长途径的定量作用。最后,尽管在这项工作中没有明确证明,但我们指出,使用我们的模型和 RNAseq 数据构建详细的蛋白质组分布是可能的,前提是已知定量的细胞分裂机制。