Gupta Abhishekh, Lloyd-Price Jason, Ribeiro Andre S
In Silico Biol. 2015;12(1-2):9-21. doi: 10.3233/ISB-140462.
Recent evidence suggests that cells employ functionally asymmetric partitioning schemes in division to cope with aging. We explore various schemes in silico, with a stochastic model of Escherichia coli that includes gene expression, non-functional proteins generation, aggregation and polar retention, and molecule partitioning in division. The model is implemented in SGNS2, which allows stochastic, multi-delayed reactions within hierarchical, transient, interlinked compartments. After setting parameter values of non-functional proteins' generation and effects that reproduce realistic intracellular and population dynamics, we investigate how the spatial organization of non-functional proteins affects mean division times of cell populations in lineages and, thus, mean cell numbers over time. We find that division times decrease for increasingly asymmetric partitioning. Also, increasing the clustering of non-functional proteins decreases division times. Increasing the bias in polar segregation further decreases division times, particularly if the bias favors the older pole and aggregates' polar retention is robust. Finally, we show that the non-energy consuming retention of inherited non-functional proteins at the older pole via nucleoid occlusion is a source of functional asymmetries and, thus, is advantageous. Our results suggest that the mechanisms of intracellular organization of non-functional proteins, including clustering and polar retention, affect the vitality of E. coli populations.
最近的证据表明,细胞在分裂过程中采用功能不对称的分配方案来应对衰老。我们利用大肠杆菌的随机模型在计算机上探索各种方案,该模型包括基因表达、无功能蛋白质的产生、聚集和极性保留,以及分裂过程中的分子分配。该模型在SGNS2中实现,它允许在分层、瞬态、相互连接的隔室内进行随机、多延迟反应。在设定能够重现现实细胞内和群体动态的无功能蛋白质产生及效应的参数值后,我们研究无功能蛋白质的空间组织如何影响谱系中细胞群体的平均分裂时间,进而影响随时间变化的平均细胞数量。我们发现,随着分配越来越不对称,分裂时间会减少。此外,增加无功能蛋白质的聚集会减少分裂时间。增加极性分离中的偏差会进一步减少分裂时间,特别是当偏差有利于较老的极且聚集体的极性保留很强时。最后,我们表明,通过类核阻塞将遗传的无功能蛋白质非能量消耗性地保留在较老的极是功能不对称的一个来源,因此是有利的。我们的结果表明,无功能蛋白质的细胞内组织机制,包括聚集和极性保留,会影响大肠杆菌群体的活力。