Individuality and slow dynamics in bacterial growth homeostasis
Individuality and slow dynamics in bacterial growth homeostasis
复制标题
细菌生长稳态的个体性和缓慢动态
DOI：
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发表时间：
2018
影响因子：
11.1
通讯作者：
N. Brenner
中科院分区：
文献类型：
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作者：
Lee Susman;M. Kohram;H. Vashistha;Jeffrey T. Nechleba;H. Salman;N. Brenner
意义微生物细胞经历重复的生长和分裂周期。这些周期并不完美：分裂的时间和规模可以从一个周期波动到下一个周期。尽管如此，细胞大小保持严格控制，波动不会积累到大的偏差。这种控制是如何在单细胞中实现的仍然没有完全理解。我们进行了实验，在微流体陷阱中跟踪单个细菌数百代。这使我们能够识别在许多生长和分裂周期中保持的独特的个体动态特性。令人惊讶的是，我们发现每个细胞都以不同的强度抑制波动;这种可变性为每个细胞定义了一种“个体”行为，这种行为是沿着许多代遗传的。微生物的生长和分裂是生命科学许多领域的基础过程。特别令人感兴趣的是体内平衡机制，它缓冲生长和分裂，使其免受多个周期的累积波动。这些机制在单个细胞内运作，可能延伸到几个分裂周期。然而，迄今为止，所有的实验研究都依赖于从许多不同的细胞汇集的测量。在这里，我们将单个细胞的长期测量痕迹从彼此中分离出来，揭示了时间统计和汇总统计之间的细微差异。通过分析沿着多达数百代的相关性，我们发现描述有效细胞大小稳态强度的参数在细胞之间变化显著。在同一时间，我们发现一个不变的细胞大小，它作为一个吸引所有个人的痕迹，虽然有不同的有效吸引力。尽管有共同的吸引子，但每个细胞在其有限的寿命内保持不同的平均大小，周围的时间波动受到抑制，并且平衡到全局平均大小令人惊讶地缓慢（>150个细胞周期）。为了显示可变稳态强度的可能来源，我们构建了一个依赖于细胞内相互作用的数学模型，该模型将细胞大小的测量特性与高表达蛋白质的测量特性相结合。有效的内稳态强度受相互作用和噪声水平的影响，并且通常在细胞之间变化。一个可预测的和可测量的后果，可变的稳态强度出现在不同的振荡模式，细胞大小和蛋白质含量在许多代。我们讨论了我们的研究结果的影响，以了解单细胞分裂的控制机制及其特征的时间尺度。
Significance Microbial cells go through repeated cycles of growth and division. These cycles are not perfect: the time and size at division can fluctuate from one cycle to the next. Still, cell size is kept tightly controlled, and fluctuations do not accumulate to large deviations. How this control is implemented in single cells is still not fully understood. We performed experiments that follow individual bacteria in microfluidic traps for hundreds of generations. This enables us to identify distinct individual dynamic properties that are maintained over many cycles of growth and division. Surprisingly, we find that each cell suppresses fluctuations with a different strength; this variability defines an “individual” behavior for each cell, which is inherited along many generations. Microbial growth and division are fundamental processes relevant to many areas of life science. Of particular interest are homeostasis mechanisms, which buffer growth and division from accumulating fluctuations over multiple cycles. These mechanisms operate within single cells, possibly extending over several division cycles. However, all experimental studies to date have relied on measurements pooled from many distinct cells. Here, we disentangle long-term measured traces of individual cells from one another, revealing subtle differences between temporal and pooled statistics. By analyzing correlations along up to hundreds of generations, we find that the parameter describing effective cell size homeostasis strength varies significantly among cells. At the same time, we find an invariant cell size, which acts as an attractor to all individual traces, albeit with different effective attractive forces. Despite the common attractor, each cell maintains a distinct average size over its finite lifetime with suppressed temporal fluctuations around it, and equilibration to the global average size is surprisingly slow (>150 cell cycles). To show a possible source of variable homeostasis strength, we construct a mathematical model relying on intracellular interactions, which integrates measured properties of cell size with those of highly expressed proteins. Effective homeostasis strength is then influenced by interactions and by noise levels and generally varies among cells. A predictable and measurable consequence of variable homeostasis strength appears as distinct oscillatory patterns in cell size and protein content over many generations. We discuss implications of our results to understanding mechanisms controlling division in single cells and their characteristic timescales.
影响因子：
1.8
作者：
Brenner, Naama;Braun, Erez;Salman, Hanna
通讯作者：
Salman, Hanna