Division in Escherichia coliis triggered by a size-sensing rather than a timing mechanism

Abstract

BackgroundMany organisms coordinate cell growth and division through size control mechanisms: cells must reach a critical size to trigger a cell cycle event. Bacterial division is often assumed to be controlled in this way, but experimental evidence to support this assumption is still lacking. Theoretical arguments show that size control is required to maintain size homeostasis in the case of exponential growth of individual cells. Nevertheless, if the growth law deviates slightly from exponential for very small cells, homeostasis can be maintained with a simple ‘timer’ triggering division. Therefore, deciding whether division control in bacteria relies on a ‘timer’ or ‘sizer’ mechanism requires quantitative comparisons between models and data.ResultsThe timer and sizer hypotheses find a natural expression in models based on partial differential equations. Here we test these models with recent data on single-cell growth of Escherichia coli. We demonstrate that a size-independent timer mechanism for division control, though theoretically possible, is quantitatively incompatible with the data and extremely sensitive to slight variations in the growth law. In contrast, a sizer model is robust and fits the data well. In addition, we tested the effect of variability in individual growth rates and noise in septum positioning and found that size control is robust to this phenotypic noise.ConclusionsConfrontations between cell cycle models and data usually suffer from a lack of high-quality data and suitable statistical estimation techniques. Here we overcome these limitations by using high precision measurements of tens of thousands of single bacterial cells combined with recent statistical inference methods to estimate the division rate within the models. We therefore provide the first precise quantitative assessment of different cell cycle models.

Longitudinal zonation pattern inArabidopsisroot tip defined by a multiple structural change algorithm

“…Cells have to reach a certain critical size at which cell-cycle transitions are triggered, such as G1-S or G2-mitosis (Ivanov, 1971;Dobrochaev and Ivanov, 2001;Dolznig et al, 2004;Yang et al, 2006;Turner et al, 2012;Robert et al, 2014). Therefore, along the PD it is expected that cells are equal to or smaller than the critical size of dividing cells (L critD ).…”

A size threshold governsCaenorhabditis elegansdevelopmental progression

“…Previous work in other organisms has suggested that there is either a timer or a body size-based trigger for moulting transitions in ecdysozoan growth [13]; this is analogous to 'Timer' versus 'Sizer' models for the proliferation of individual cells [14,15]. For example, the hormone ecdysone has been shown to be a secreted signal important for the timing of larval stage transitions in the moth Manduca sexta.…”

A surprising range of modified-methionyl S-adenosylmethionine analogues support bacterial growth

“…In each case, to facilitate comparison, 500 cells are plotted (see Methods for details), and their size is plotted versus their rank from smallest to largest. Variation in size is expected, with cells immediately predivision having twice the length (but the same width) as cells immediately post-division (Robert et al, 2014).…”

“…This allowed calculation of cell areas in the plane of the micrograph. As E. coli cell widths are essentially constant at a given growth rate (Pierucci, 1978;Robert et al, 2014), area is proportional to length. For E. coli strains B/r and MG1655 (K-12) growing in rich media, those studies reported widths of 0.87 and up to 0.95 mm, respectively.…”