Analysis of protein synthesis dynamic model in eukaryotic cells: Input control

Area of Science:

• Mathematical Biology
• Molecular Biology
• Systems Biology

Background:

• Protein synthesis is a fundamental cellular process.
• Regulation of protein synthesis is crucial for cell function and disease.
• Eukaryotic initiation factor 2 (eIF-2) plays a key role in initiating protein synthesis.

Purpose of the Study:

• To analyze and propose control methods for the protein synthesis initiation model based on eIF-2.
• To simplify the complex non-linear model through linearization for control applications.
• To investigate the effects of key regulatory factors and develop a control strategy for protein synthesis rate.

Main Methods:

• Linearization of the non-linear protein synthesis initiation model.
• Simulation-based comparison of linear and non-linear models.
• Application of linear optimal control theory.
• Analysis of input signals (GCN2.tRNA, eIF-2) on the non-linear system.
• State feedback control design.

Main Results:

• The linearized model was found to be marginally stable with states converging to finite values.
• Overexpression of eIF-2 was shown to increase 48S initiation complex concentration and promote initiation rate, consistent with experimental findings.
• A state feedback control strategy was successfully designed to manipulate the initiation rate by controlling the 48S initiation complex concentration.

Conclusions:

• The linearized model provides a valid approximation for control design within a specific range.
• Mathematical analysis confirmed experimental observations regarding eIF-2 function and its impact on protein synthesis initiation.
• A viable state feedback control strategy was demonstrated for precise manipulation of protein synthesis rates, paving the way for potential therapeutic interventions.