A Markovian Approach towards Bacterial Size Control and Homeostasis in Anomalous Growth Processes

Yanyan Chen,Rosa Baños,Javier Buceta

doi:10.1038/s41598-018-27748-9

Yanyan Chen, Rosa Baños + Show 1 more

Open Access

https://doi.org/10.1038/s41598-018-27748-9

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Abstract

Regardless of the progress achieved during recent years, the mechanisms coupling growth and division to attain cell size homeostasis in bacterial populations are still not well understood. In particular, there is a gap of knowledge about the mechanisms controlling anomalous growth events that are ubiquitous even in wild-type phenotypes. Thus, when cells exceed the doubling size the divisome dynamics sets a characteristic length scale that suggests a sizer property. Yet, it has been recently shown that the size at birth and the size increment still satisfy an adder-like correlation. Herein we propose a Markov chain model, that we complement with computational and experimental approaches, to clarify this issue. In this context, we show that classifying cells as a function of the characteristic size set by the divisome dynamics provides a compelling framework to understand size convergence, growth, and division at the large length scale, including the adaptation to, and rescue from, filamentation processes. Our results reveal the independence of size homeostasis on the division pattern of long cells and help to reconcile sizer concepts at the single cell level with an adder-like behavior at a population level.

Highlights

To the idea that memory effects could play a role in size regulation and homeostasis[24]
Experiments on ΔminC strains have shown that the positioning of the septum is not relevant at the short length scale either to satisfy the adder correlation[8]. We focus on these questions and, by combining theoretical, computational, and experimental work, we address the problem of understanding how large size fluctuations contribute to size regulation
In a regular growth/division process a size increment of the order l0 + Δl0 is achieved, where Δl0 accounts for the variability around the characteristic length l0, i.e. the relative fluctuations in the growth of daughter cells with respect the mother cell are of order Δl0/l0, Fig. 1a

Summary

Introduction

To the idea that memory effects could play a role in size regulation and homeostasis[24]. A recent study in the context of cell filamentation has suggested that the adder principle may have a wider applicability and poses the interesting problem of making it compatible with a sizer behavior that quantizes the division locations[28] This problem applies to wild-type cells, since subpopulations that deviate from typical sizes are ubiquitous and yet size homeostasis is achieved. If division fails and cells grow longer, multiple rings are formed at regular intervals along the cell determining multiple, putative, cleavage sites[36] This poses the intriguing question of understanding what is the influence of the division pattern for setting a cell size distribution and for enabling size convergence. Our study helps to reconcile concepts and shows that, at the large length scale, a sizer feature at the single-cell level, i.e. to consider a well defined length scale associated with division events, is compatible with the experimental observations about the adder correlations at the population level

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