A Dynamical Model for Heat Shock Protein (HSP) Transcription and its Correlation with HSP70 in vitro Experiments

Abstract

Heat-shock proteins (HSPs) are well know for their protective mechanism when cells undergo stress conditions such as heat by enhancing protein folding and mitigating apoptosis Heat-shock causes the denaturing of proteins to increase, which leads to the aggregation of denatured and functional proteins. On the other hand, cells develop thermotolerance to protect themselves from later exposure to heat shock or other stresses. Once a cell has been exposed to the heat-shock, the fate of the cell depends on the amount of protein denaturation and aggregation. The cell's ability to become tolerant of heat after the heat-shock is one of the most widely studied activating responses experimentally. In the paper, we develop three mechanistic models in a hierarchical fashion that follow a biological pathway from the initial heat-shock to the HSP70:HSF complex that dissociates to HSP70 and HSF, and aim to predict the HSP concentration in a cell. These models allow investigators to simulate the major/important mechanisms in the upregulation of HSP70. This study was performed to create a depiction of the cellular and nuclear events of the HSP70 response to the heat-shock. The data generated from the model were correlated to favorably experimental data under the assumption of time delay.