Programmable Coacervate-Membrane Interactions Direct Internal and Collective Organization in Membranized Protocells

Area of Science:

• Biomimetic engineering
• Synthetic biology
• Cellular organization

Background:

• Eukaryotic cells utilize membraneless organelles that interact with the plasma membrane and cortex.
• Cytoskeletal coupling and membrane biochemistry regulate organelle positioning, wetting, and function.
• Recreating adaptive, cortex-mediated control in synthetic systems is challenging.

Purpose of the Study:

• To introduce a synthetic chassis for programmable coacervate-membrane coupling.
• To develop mechanically robust protocells with interfacial programmability.
• To achieve fine control over coacervate wetting, morphology, and spatial organization.

Main Methods:

• Introduction of polysaccharidosomes (P-somes) as semipermeable, mechanically robust protocells.
• Establishment of a cortex-like protein layer on the inner membrane leaflet via template-directed assembly.
• In situ protein succinylation for tuning surface charge and coacervate-membrane wetting.
• Systematic variation of membrane building blocks and uptake of external DNA for regulation.

Main Results:

• Demonstrated precise tuning of surface charge and coacervate-membrane wetting through protein succinylation.
• Achieved fine control over coacervate wetting, morphology, and spatial organization.
• Showcased DNA-mediated regulation of coacervate behavior, leading to tissue-like clustering or nucleus-like droplet formation.

Conclusions:

• The developed platform integrates mechanical resilience with chemical programmability.
• This framework offers a scalable route to constructing membranized protocells with self-organizing interiors.
• Emergent collective behaviors were observed in the synthetic protocell system.