基于细胞间变异性分析重新评估细胞大小控制的基础
Reassessment of the basis of cell size control based on analysis of cell-to-cell variability
摘要：
对细胞大小控制和体内平衡的基本机制仍然知之甚少。单细胞分裂和出生时大小之间的关系被用作对大小稳态基础进行分类的度量[1-3]。以固定大小分裂的细胞（无论出生大小（sizer））预期显示分裂-出生斜率为0，而在生长固定大小增量（adder）后分裂的细胞预期斜率为+1 [4]。然而，这两个理论值很少在实验中观察到。例如，杆状分裂酵母$\it{Schizosaccharomyces}$ $\it{pombe}$细胞在固定的表面积上分裂[5，6]，细胞长度的分裂-出生斜率为0.25 $\pm$ 0.02，与预期的尺寸值0显著不同。在这里，我们调查可能的原因，这种差异，通过开发一个数学模型的尺寸控制，包括相关的变化来源。我们的结果支持$\it{pure}$测瓣器控制，并表明通过测量不适当的几何量（例如，长度而不是面积），结合细胞到细胞的半径可变性。该模型预测，突变体与更大的错误，在尺寸传感或隔膜定位矛盾的表现更好的sizers。此外，占细胞宽度的变化，我们表明，纯尺寸控制可以在某些情况下重现明显的加法器行为观察到的$\it{E. coli}$。这些发现表明，几何变化的分析可以导致细胞大小控制的新见解。
英文摘要：
Fundamental mechanisms governing cell size control and homeostasis are still poorly understood. The relationship between sizes at division and birth in single cells is used as a metric to categorize the basis of size homeostasis [1-3]. Cells dividing at a fixed size regardless of birth size (sizer) are expected to show a division-birth slope of 0, whereas cells dividing after growing for a fixed size increment (adder) have an expected slope of +1 [4]. These two theoretical values are, however, rarely experimentally observed. For example, rod-shaped fission yeast $\it{Schizosaccharomyces}$ $\it{pombe}$ cells, which divide at a fixed surface area [5, 6], exhibit a division-birth slope for cell lengths of 0.25$\pm$0.02, significantly different from the expected sizer value of zero. Here we investigate possible reasons for this discrepancy by developing a mathematical model of sizer control including the relevant sources of variation. Our results support $\it{pure}$ sizer control and show that deviation from zero slope is exaggerated by measurement of an inappropriate geometrical quantity (e.g., length instead of area), combined with cell-to-cell radius variability. The model predicts that mutants with greater errors in size sensing or septum positioning paradoxically appear to behave as better sizers. Furthermore, accounting for cell width variability, we show that pure sizer control can in some circumstances reproduce the apparent adder behaviour observed in $\it{E. coli}$. These findings demonstrate that analysis of geometric variation can lead to new insights into cell size control.
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