Model of Eukaryotic Cell Protein Control Schemes via Manufacturing System Simulator

The folding and transport of proteins in the Endoplasmic Reticulum (ER) of mammalian cells exhibit similarities to industrial manufacturing processes, in that they are complex systems regulated by control mechanisms. Recently, two such control systems have been identified: the Unfolded Protein Response (UPR) and AutoRegulation of ER eXport (AREX), which allow the ER to adapt to fluctuations and stress. However, the challenges of modeling their activities arise from the lack of data and the complexity of the signaling pathways that activate them. In this study, we utilize a simulation tool commonly employed in manufacturing plants to develop a model that replicates the protein production process in the ER and the actions of the UPR and AREX in mitigating stress conditions. Our simulations provide insights into the behavior of the cell and represent the first attempt to integrate the entire protein production process and the control activity in the ER. The simulation results demonstrate the potential of regarding the ER as a manufacturing process and provide a novel approach to understanding the complex regulation of the ER.