Chemically programmed multistage morphogenesis in coacervate microdroplets
- 1State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University
Abstract
Chemical reaction-driven morphogenesis enables adaptive membraneless organelles to translate biochemical inputs into coordinated structural and functional responses autonomously, but achieving non-equilibrium morphogenesis in synthetic coacervates remains challenging. Here we report an oxidation programmed multistage morphogenesis in coacervate microdroplets composed of polyethyleneimine (PEI) and sodium thioctate (ST). Coacervate microdroplets form through electrostatic complexation between PEI and ST, together with hydrophobic association among the dithiolane motifs of ST. Hydrogen peroxide converts these dithiolane motifs into more polar species, progressively weakening hydrophobic clustering, increasing hydration within the coacervate phase, and driving the microdroplets away from their initial equilibrium state. This reaction-induced compositional imbalance drives initially homogeneous microdroplets to evolve into multivacuolated intermediates, hollow structures, and finally contracted microdroplets. Experimental and simulation results support a reaction-induced secondary phase separation in which ST oxidation promotes secondary phase separation, osmotic water uptake, vacuole growth, coalescence, and shell remodeling. By recruiting glucose oxidase (GOx) into the coacervate phase to generate H2O2 in situ, we further establish an enzyme-driven route in which glucose autonomously actuates a similar sequence of multistage morphogenesis. Coupling the GOx/glucose pathway with the horseradish peroxidase/Amplex Red cascade reaction further linked glucose-triggered morphogenesis to fluorescent signal generation, enabling coacervate microdroplets to integrate biochemical sensing, structural remodeling, and optical readout. Overall, this work establishes a reaction-induced secondary phase separation for programming life-like multistage morphogenesis in membraneless microcompartments.
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BibTeX
@misc{li2026chemically,
title = {{Chemically programmed multistage morphogenesis in coacervate microdroplets}},
author = {J. Li and H. Yu and Y. Duan and B. Yang and X. Zeng and Y. Li},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.16.745086},
url = {https://www.biorxiv.org/content/10.64898/2026.08.16.745086v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Chemically programmed multistage morphogenesis in coacervate microdroplets
AU - J. Li
AU - H. Yu
AU - Y. Duan
AU - B. Yang
AU - X. Zeng
AU - Y. Li
PY - 2026
DA - 2026/08/16
PB - bioRxiv
DO - 10.64898/2026.08.16.745086
UR - https://www.biorxiv.org/content/10.64898/2026.08.16.745086v2
AB - Chemical reaction-driven morphogenesis enables adaptive membraneless organelles to translate biochemical inputs into coordinated structural and functional responses autonomously, but achieving non-equilibrium morphogenesis in synthetic coacervates remains challenging. Here we report an oxidation programmed multistage morphogenesis in coacervate microdroplets composed of polyethyleneimine (PEI) and sodium thioctate (ST). Coacervate microdroplets form through electrostatic complexation between PEI and ST, together with hydrophobic association among the dithiolane motifs of ST. Hydrogen peroxide converts these dithiolane motifs into more polar species, progressively weakening hydrophobic clustering, increasing hydration within the coacervate phase, and driving the microdroplets away from their initial equilibrium state. This reaction-induced compositional imbalance drives initially homogeneous microdroplets to evolve into multivacuolated intermediates, hollow structures, and finally contracted microdroplets. Experimental and simulation results support a reaction-induced secondary phase separation in which ST oxidation promotes secondary phase separation, osmotic water uptake, vacuole growth, coalescence, and shell remodeling. By recruiting glucose oxidase (GOx) into the coacervate phase to generate H2O2 in situ, we further establish an enzyme-driven route in which glucose autonomously actuates a similar sequence of multistage morphogenesis. Coupling the GOx/glucose pathway with the horseradish peroxidase/Amplex Red cascade reaction further linked glucose-triggered morphogenesis to fluorescent signal generation, enabling coacervate microdroplets to integrate biochemical sensing, structural remodeling, and optical readout. Overall, this work establishes a reaction-induced secondary phase separation for programming life-like multistage morphogenesis in membraneless microcompartments.
ER -