Stabilization control of small heat shock proteins in cellular chaperone protection systems

The role of small heat shock proteins (sHsps) in the cellular chaperone system was examined with application of the feedback control technique widely used in engineering for stabilizing a specific system. We proposed a dynamic feedback control model for the thermotolerance machinery of sHsps from the system biology perspective, and for the first time verified that a system stabilization feedback control scheme is involved in the chaperone protecting activity under heat shock conditions. In the dynamic model of the chaperone protection system, the defense mechanism of sHsps is a sigmoid function and the influence of environment temperatures is a bell-shaped function. The close fit of the system dynamic behaviors to the kinetic data suggests that our system stabilization control model matches the protective mechanism conveyed by sHsps. Furthermore, the temporal changes of the unfolded intermediates and the sHsp-substrate complexes can be predicted by the proposed dynamic stabilization model, which are not easily measured in biochemical experiments. The identified feedback control matrix can be viewed as a biochemical interaction for measuring the protective activity of sHsps qualitatively and quantitatively. Our work introduces an innovative approach for analysis and detecting the kinetics of sHsps to resist protein aggregation from the system stabilization point of view.