Exploring mechanisms for bacterial width change using coarse-grained simulations of the peptidoglycan cell wall

Abstract

Rod-like bacteria control cell width with high precision during growth. For a given species and growth medium, the variation in cell widths in a population is only about 5%. At the same time, the widths appear flexible when the cells are subjected environmental perturbations by changing their cell widths into a new steady state quickly. Despite decades of research on cell shape, how cells display such precise width control while also showing pliancy upon environmental perturbations remains unknown. Previous experiments have shown that the peptidoglycan (PG) cell wall is the major contributor to resisting the high intracellular pressures in the cell by forming a rigid scaffold around the cell. During growth, new PG is inserted into the cell wall and old material is broken down. Together, these processes result in the dynamic equilibrium that determines cell shape. To understand the effects of cell wall remodelling and PG topology on width homeostasis, we conducted coarse- grained computational simulations that mimic the cell wall and the processes of PG synthesis and breakdown. Different from previous simulations of whole-cell sacculi, we restrict our simulation to a small periodic patch of PG with dynamic boundaries that mimic the high intracellular turgor pressure. This allows for fast computation and thus for the systematic investigation of model parameters, e.g., the rates of cutting and insertion. Our computational simulations then allow us to systematically test different mechanisms of PG insertion and breakdown for their ability to decrease or increase cell width over time. We show that insertions of long, unstretched glycan strands when coupled with cutting of nearby PG bonds is sufficient to constrict the width of the cell over many generations, and the inhibition of such insertions results in an increase in cell widths.