Mimicking Cellular Compartmentalization in a Hierarchical Protocell through Spontaneous Spatial Organization

Area of Science:

• Synthetic Biology
• Biomimetic Chemistry
• Materials Science

Background:

• Eukaryotic cells exhibit spatial organization via compartmentalization.
• Developing protocells with synthetic organelles is key to mimicking cellular life.
• Compartmentalization enables efficient biochemical reactions and protects cellular components.

Purpose of the Study:

• To demonstrate the bottom-up assembly of subcompartmentalized protocells.
• To create a system mimicking cellular cytosol and membrane structure.
• To investigate the impact of spatial organization on protocell functionality.

Main Methods:

• Spontaneous encapsulation of polymersome proto-organelles within cell-sized coacervates.
• Membranization of coacervate microdroplets using tailor-made terpolymers.
• Hierarchical self-assembly of protocell structures.

Main Results:

• Successfully formed rudimentary subcompartmentalized protocells.
• Achieved fine-tuned spatial organization of enzymes, enhancing functionality.
• Demonstrated sequestration of incompatible components without detrimental effects.
• Confirmed robust stability in biocompatible media (PBS, cell culture media).

Conclusions:

• The developed coacervate protocells mimic key cellular features like condensed cytosol and cell membranes.
• This platform offers enhanced functionality through controlled enzyme localization.
• The system provides a versatile foundation for in vitro and potential in vivo studies.