4.7 Article

Biomimetic Cell Structures: Probing Induced pH-Feedback Loops and pH Self-Monitoring in Cytosol Using Binary Enzyme-Loaded Polymersomes in Proteinosome

Journal

BIOMACROMOLECULES
Volume 24, Issue 6, Pages 2489-2500

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.3c00010

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Researchers have successfully constructed giant multicompartment protocells with structures and functions similar to eukaryotic cells, and encapsulated pH-responsive polymersomes and enzymes into them. This system can probe biomimetic pH homeostasis.
Structures and functions of eukaryotic cells with anouter permeablemembrane, a cytoskeleton, functional organelles, and motility canbe mimicked by giant multicompartment protocells containing varioussynthetic organelles. Herein, two kinds of artificial organelles withstimuli-triggered regulation ability, glucose oxidase-(GOx)-loadedpH-responsive polymersomes A (GOx-Psomes A) and urease-loaded pH-responsivepolymersomes B (Urease-Psomes B), and a pH-sensor (Dextran-FITC) areencapsulated into proteinosomes via the Pickering emulsion method.Thus, a polymersomes-in-proteinosome system is constructed which isable to probe biomimetic pH homeostasis. Alternating fuels (glucoseor urea) introduced from outside the protocell penetrate the membraneof proteinosomes and enter into GOx-Psomes A and Urease-Psomes B toproduce chemical signals (gluconic acid or ammonia) resulting in pH-feedbackloops (pH jump and pH drop). This will counteract the catalytic switchon or switch off of enzyme-loaded Psomes Aand B owing to their different pH-responsive membranes. Dextran-FITCin the proteinosome allows self-monitoring of slight pH fluctuationsin the lumen of protocells. Overall, this approach shows heterogeneouspolymersome-in-proteinosome architectures with sophisticated featuressuch as input-regulated pH changes mediated by negative and positivefeedback in loops and cytosolic pH self-monitoring, features thatare imperative for advanced protocell design.

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