How Transcriptional Bursting and mRNA Production Affect Precise Timing of Cell Lysis Phenomena.

Abstract

Bacterial viruses infect bacterial cells and stimulate the production of holin proteins that accumulate in the cellular membranes. When the number of such proteins reaches a threshold, the membrane permeabilizes and the cell is destroyed in the process known as cell lysis. Experimental studies indicate that cell lysis occurs at specific times, although the underlying molecular mechanisms of such precise timing remain not well understood. Recently, a theoretical framework has been introduced to explain these phenomena as a coupling between stochastic processes of holins accumulation in the membrane and breaking the membrane that leads to threshold behavior. However, this approach does not account for many biologically important processes in cell lysis. In this work, we investigated the role of transcriptional bursting and mRNA production on the dynamics of cell lysis. The original stochastic framework is extended, allowing us to evaluate the cell lysis dynamics under more realistic biological conditions using analytical calculations and Monte Carlo computer simulations. It is shown explicitly that the random processes of transcription bursting and mRNA production do not affect the threshold-like dynamics of cell lysis, although they influence the absolute values of the maximal thresholds and their distributions. It is also found that the effect of mRNA production is generally stronger than the effect due to transcriptional bursting. Physical-chemical arguments to explain these observations are presented. Thus, our theoretical analysis suggests that the precise timing of cell lysis is a robust phenomenon despite involving multiple random biochemical processes. Our theoretical approach clarifies some important mechanistic aspects of complex biological processes of cell lysis.