# Reassessment of the basis of cell size control based on analysis of cell-to-cell variability

## TL;DR

This study revisits cell size control mechanisms, showing that apparent deviations from theoretical models can be explained by measurement choices and cell variability, supporting the pure sizer model.

## Contribution

The paper develops a mathematical model incorporating cell-to-cell variability, clarifying how measurement and biological factors influence observed size control behaviors.

## Key findings

- Pure sizer control is supported by the model.
- Measurement of geometrical quantities affects observed slopes.
- Cell width variability can mimic adder behavior.

## Abstract

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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Source: https://tomesphere.com/paper/1902.04826