Modeling the Impact of Spatial Localization of Protein Function in the Endoplasmic Reticulum of Yeast

Protein-protein interactions underlie the fundamental processes of every cell. Certain proteins called chaperones specialize in protein folding, maturation, and degradation functions within a cell. BiP is the resident chaperone in the endoplasmic reticulum (ER) of eukaryotic cells. Following adverse cellular conditions, BiP acts as a mediator in returning the cell to homeostasis. Spatial localization of BiP in the ER is also thought to impact its function, as it can interact with proteins on the ER membrane and in the ER interior (lumen). Our focus is on the process of translocation, in which BiP assists in the transport of nascent proteins through membrane channels into the lumen. A deterministic model has been created to represent the system as a set of reaction-diffusion equations in order to explore the spatial distribution (and localization) of BiP under various experimental scenarios. Further analysis has underscored the need for stochastic modeling using methods such as Gillespie's Stochastic Simulation Algorithm (SSA). Comparisons of these deterministic and stochastic simulations are presented along with an investigation of the interplay of kinetic, diffusion, and geometric parameters of system behavior represented by these models.