A mechanistic stochastic framework for regulating bacterial cell division.
A mechanistic stochastic framework for regulating bacterial cell division.
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DOI：
10.1038/srep30229
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发表时间：
2016-07-26
影响因子：
4.6
通讯作者：
Singh A
中科院分区：
文献类型：
--
作者：
Ghusinga KR;Vargas-Garcia CA;Singh A
呈指数增长的细胞如何维持大小稳态是一个重要的基本问题。最近对原核生物的单细胞研究揭示了加法器原理，即细胞从出生到分裂增加固定的大小（体积），无论其出生时的大小如何。为了从机械上解释加法器原理，我们考虑一种计时器蛋白，它在细胞诞生后开始以与体积成比例的速率随机表达。细胞分裂时间被公式化为蛋白质拷贝数达到固定阈值的首次传代时间。与数据一致，该模型预测分裂时间中的噪声随着出生时体型的大小而增加。有趣的是，我们的结果表明，连续细胞分裂事件之间增加的体积分布与新生细胞的大小无关。这在实验研究中得到了戏剧性的体现，其中与不同新生儿尺寸相对应的增加体积的直方图相互重叠。该模型提供了与实验观察结果一致的进一步见解：按平均值缩放时添加体积的分布变得与增长率保持不变。总之，我们简单而优雅的模型解释了关键的实验结果，并提出了一种调节细胞分裂时间的平均值和波动以控制大小的机制。
How exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells add a fixed size (volume) from birth to division, irrespective of their size at birth. To mechanistically explain the adder principle, we consider a timekeeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that the noise in division timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distribution of the added volume when scaled by its mean becomes invariant of the growth rate. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for controlling size.