Department of Molecular and Cellular Biology, Center for Systems Biology, Harvard University, Cambridge, MA, USA.
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Nat Microbiol. 2018 Feb;3(2):148-154. doi: 10.1038/s41564-017-0082-6. Epub 2017 Dec 18.
In nature, microorganisms exhibit different volumes spanning six orders of magnitude . Despite their capability to create different sizes, a clonal population in a given environment maintains a uniform size across individual cells. Recent studies in eukaryotic and bacterial organisms showed that this homogeneity in cell size can be accomplished by growing a constant size between two cell cycle events (that is, the adder model ). Demonstration of the adder model led to the hypothesis that this phenomenon is a consequence of convergent evolution. Given that archaeal cells share characteristics with both bacteria and eukaryotes, we investigated whether and how archaeal cells exhibit control over cell size. To this end, we developed a soft-lithography method of growing the archaeal cells to enable quantitative time-lapse imaging and single-cell analysis, which would be useful for other microorganisms. Using this method, we demonstrated that Halobacterium salinarum, a hypersaline-adapted archaeal organism, grows exponentially at the single-cell level and maintains a narrow-size distribution by adding a constant length between cell division events. Interestingly, the archaeal cells exhibited greater variability in cell division placement and exponential growth rate across individual cells in a population relative to those observed in Escherichia coli . Here, we present a theoretical framework that explains how these larger fluctuations in archaeal cell cycle events contribute to cell size variability and control.
在自然界中,微生物的体积跨度达到了六个数量级。尽管它们能够创造出不同的大小,但在给定的环境中,一个克隆群体的每个细胞仍保持着相同的大小。最近在真核生物和细菌中的研究表明,细胞大小的这种均一性可以通过在两个细胞周期事件之间生长一个恒定的大小来实现(即加法器模型)。加法器模型的证明导致了这样一种假设,即这种现象是趋同进化的结果。鉴于古菌细胞与细菌和真核生物都具有相似的特征,我们研究了古菌细胞是否以及如何控制细胞大小。为此,我们开发了一种软光刻方法来培养古菌细胞,以实现定量的延时成像和单细胞分析,这对于其他微生物也是有用的。使用这种方法,我们证明了嗜盐古菌(一种适应高盐的古菌)在单细胞水平上呈指数生长,并通过在细胞分裂事件之间添加一个恒定的长度来维持狭窄的大小分布。有趣的是,与在大肠杆菌中观察到的情况相比,古菌细胞在细胞分裂位置和指数生长率方面在群体内的个体细胞之间表现出更大的可变性。在这里,我们提出了一个理论框架,解释了古菌细胞周期事件中的这些更大波动如何导致细胞大小的可变性和控制。