Autonomous Self-Pulsation of Protein Vesicles via Substrate-Induced Protein Allosteric Cycle

Area of Science:

• Biomimetic systems
• Synthetic biology
• Biophysics

Background:

• Oscillatory phenomena are fundamental to biological systems, driving essential life rhythms like cardiac pulsation.
• Replicating biotic oscillations is key for creating lifelike systems and achieving periodic chemical-to-mechanical energy conversion in vitro.
• Existing synthetic systems often lack the autonomous, rhythmic behavior observed in nature.

Purpose of the Study:

• To engineer a protein-based vesicle system capable of autonomous, rhythmic pulsation.
• To demonstrate substrate-induced control over the oscillation dynamics and properties.
• To explore the potential for programmed transmembrane transport in synthetic assemblies.

Main Methods:

• Assembling protein kinase-polypeptide mega-amphiphiles into vesicular structures (proteinosomes).
• Utilizing an allosteric cycle triggered by specific substrates (ATP and AMP) to induce conformational changes.
• Modulating substrate concentrations to control oscillation parameters.

Main Results:

• The proteinosome system exhibited rhythmic shrinking and swelling, demonstrating autonomous pulsation in a nonequilibrium state.
• Kinase conformational changes, driven by substrate binding, were responsible for the cyclical motion.
• Oscillation characteristics (periodicity, amplitude, lifetime) were tunable by controlling substrate levels.
• The oscillation was shown to periodically alter membrane permeability.

Conclusions:

• A novel protein-based vesicle system capable of autonomous, rhythmic pulsation has been developed.
• The system's oscillation is driven by a substrate-induced protein allosteric cycle, offering precise control.
• This work provides a foundation for synthetic systems with programmable transport and lifelike dynamic behaviors.