Stochastic Simulation of Stress Granules

Cells form stress granules (SGs) in response to various forms of environmental stress, including heat shock, radiation, low oxygen pressure, chemicals such as arsenite, and viral infections. SGs are nonmembranous aggregates composed of mRNAs and their binding proteins. The role of SGs is hypothesized as loci for the storage and/or sorting mRNAs leading to reuse or degradation. The number of SGs in a cell as well as their locations and temporal speed of formation are critical elements in determining cell fate. Although extensive studies have been carried out to examine the dynamics of SG formation, factors controlling the dynamics are still largely unknown. We approached this problem by utilizing computer simulation. However, the commonly used simulation method, deterministic simulation (DS), cannot be applied to SGs. DS is valid in the case of large numbers of molecules of the order of Avogadro’s number, as DS employs concentration to express the abundance of molecules. Because only several tens of SGs are present in a single cell, their abundance is preferably expressed in terms of their number. Thus, we applied the method of stochastic simulation (SS). Among various methodologies of SS, we employed our own approach, whereby the coordinates and state of single molecules, which indicate whether the molecules are bound to other molecules forming a complex or unbounded as an original species, are controlled. In this chapter, we introduce our SS method and its application to SG formation. The simulation results agreed well with experimental observations and presented possible mechanisms controlling SG formation.