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pH-Driven Compartmentalization in Coacervate Protocells Enables Programmable Microreactors.

Bingzhao Wu1,2, Lianning Li2, Hu Huang2

  • 1School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, China.

Small (Weinheim an Der Bergstrasse, Germany)
|September 27, 2025
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Summary
This summary is machine-generated.

Researchers created artificial cells that change their internal structure in response to pH. These pH-adaptive protocells act as efficient microreactors for biochemical reactions, mimicking cellular functions.

Keywords:
coacervate dropletsenzymatic reactions regulationliquid–liquid phase separationmicroreactorssynthetic protocells

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Area of Science:

  • Synthetic Biology
  • Biochemistry
  • Materials Science

Background:

  • Bottom-up construction of artificial cells is crucial for understanding protocell evolution.
  • Developing functional protocell models requires efficient methods for creating responsive microcompartments.

Purpose of the Study:

  • To develop a streamlined method for constructing pH-adaptive protocells.
  • To engineer protocells capable of functioning as microreactors for cascade biochemical reactions.

Main Methods:

  • Utilized liquid-liquid phase separation (LLPS) of poly(diallyldimethylammonium chloride) (PDDA) and adenosine triphosphate (ATP) to form coacervate microdroplets.
  • Self-assembled phospholipid semipermeable membranes around coacervates.
  • Manipulated pH to alter ATP hydrolysis, modulating coacervate surface charge, surface potential, and interfacial tension, inducing secondary phase separation and dynamic microcompartments.

Main Results:

  • Successfully constructed pH-adaptive protocells via LLPS of PDDA and ATP.
  • Demonstrated that pH changes induce secondary phase separation, creating reconfigurable internal microcompartments.
  • Showcased coupling of biocatalysis with structural dynamics, where enzymatic reactions drive pH-mediated micro-compartmentalization.

Conclusions:

  • The engineered protocell model exhibits programmable dynamic micro-compartmentalization.
  • This model serves as an efficient microreactor for cascade biochemical reactions.
  • Offers potential applications in cellular mimicry, synthetic protobiology, and artificial biomolecular microreactors.