Sliding mode controller-observer pair for p53 pathway

Area of Science:

• Biomedical Engineering
• Control Theory
• Cancer Research

Background:

• Wild-type p53 protein, a crucial anti-tumor agent, is often lost in early cancerous cells.
• Restoring p53 levels using small molecule drugs is a key therapeutic strategy.
• Conventional sliding mode control (SMC) generates discontinuous control signals unsuitable for continuous drug infusion.

Purpose of the Study:

• To design a robust, non-linear control strategy for p53 drug design.
• To develop a smooth control signal for continuous drug administration using dynamic SMC (DSMC).
• To estimate unknown system states using a reduced-order sliding mode observer.

Main Methods:

• A control-oriented p53 model was developed.
• Dynamic Sliding Mode Control (DSMC) was designed for smooth control input.
• A reduced-order sliding mode observer was employed for state estimation.
• Robustness was tested against input disturbance and parametric uncertainty.

Main Results:

• The proposed DSMC technique effectively achieves sustained p53 levels through controlled drug administration.
• The boundedness of the zero-dynamics was mathematically proven.
• In-silico trials confirmed the effectiveness of the control scheme.
• DSMC demonstrated comparable performance to conventional SMC but with lower energy consumption.

Conclusions:

• DSMC provides a robust and efficient method for controlling drug delivery to maintain therapeutic p53 levels.
• The developed observer accurately estimates system states for model-based control.
• This approach offers a promising strategy for cancer therapy through precise drug administration.