Necessary and sufficient condition for hysteresis in the mathematical model of the cell type regulation of Bacillus subtilis

TL;DR

This paper develops a mathematical model to understand and control the hysteresis in cell state switching of Bacillus subtilis, linking environmental factors to biofilm formation and colony growth.

Contribution

It provides necessary and sufficient conditions for hysteresis in a minimal differential equation model of B. subtilis cell type regulation, integrating environmental inputs.

Findings

Hysteresis conditions clarify stable switching between cell states.

Environmental pH influences cell state control in the model.

Model predictions align with experimental observations.

Abstract

The key to a robust life system is to ensure that each cell population is maintained in an appropriate state. In this work, a mathematical model was used to investigate the control of the switching between the migrating and non-migrating states of the Bacillus subtilis cell population. In this case, the motile cells and matrix producers were the predominant cell types in the migrating cell population and non-migrating state, respectively, and could be suitably controlled according to the environmental conditions and cell density information. A minimal smooth model consisting of four ordinary differential equations was used as the mathematical model to control the B. subtilis cell types. Furthermore, the necessary and sufficient conditions for the hysteresis, which pertains to the change in the pheromone concentration, were clarified. In general, the hysteretic control of the cell state enables stable switching between the migrating and growth states of the B. subtilis cell population, thereby facilitating the biofilm life cycle. The results of corresponding culture experiments were examined, and the obtained corollaries were used to develop a model to input environmental conditions, especially, the external pH. On this basis, the environmental conditions were incorporated in a simulation model for the cell type control. In combination with a mathematical model of the cell population dynamics, a prediction model for colony growth involving multiple cell states, including concentric circular colonies of B. subtilis, could be established.