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Combinatorial engineering of bulk-assembled monodisperse coacervate droplets towards logically integrated protocells

Qingchuan Li, Qingchun Song, Jing Wei, Yang Cao, Dairong Chen, Ho Cheung Shum
doi: https://doi.org/10.1101/2021.02.19.432011
Qingchuan Li
1School of Chemistry & Chemical Engineering, National Engineering Research Center for Colloidal Materials, Shandong University, Jinan 250100, P. R. China.
2Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
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  • For correspondence: ashum@hku.hk cdr@sdu.edu.cn lqc3038@hku.hk
Qingchun Song
2Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
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Jing Wei
1School of Chemistry & Chemical Engineering, National Engineering Research Center for Colloidal Materials, Shandong University, Jinan 250100, P. R. China.
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Yang Cao
2Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
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Dairong Chen
1School of Chemistry & Chemical Engineering, National Engineering Research Center for Colloidal Materials, Shandong University, Jinan 250100, P. R. China.
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  • For correspondence: ashum@hku.hk cdr@sdu.edu.cn lqc3038@hku.hk
Ho Cheung Shum
2Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
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  • For correspondence: ashum@hku.hk cdr@sdu.edu.cn lqc3038@hku.hk
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Abstract

The emergence of life requires the appropriate integration of protometabolisms, compartments, and protogenomes from an intricate interplay of non-living constituents. Unveiling the mechanism of how life-related building blocks are logically integrated towards life from a high diversity of inanimate matter is an ongoing challenging task of current science. Various compartments such as lipid vesicles and coacervates have been proposed as possible microcontainers to hold prebiotic genetic materials and metabolic reactions for the construction of integrated systems. However, the spontaneous assembly of these compartments allows no selective and logical integration from a high diversity of inanimate matter, thus making the appropriate integration of the inanimate towards membranous life more a coincident and low probability event. Herein, we show that the assembly of colloidal particles with coacervate-forming molecules provides a combinatorial approach for the regularization of matter of chaos towards protocells with cellular hallmarks of size uniformity, logical integration, and unilamellar membransation. Monodisperse coacervate droplets coated by colloidal particles are assembled through hydrodynamic forcing-promoted coalescence. Using these coacervates as platform, a combinatorially integrative approach is developed to engineer the complexity of coacervates, from coacervate entities with programmable spatial loading to diverse interconnected coacervate consortia with collective morphology evolution. A fluidic unilamellar membrane is assembled on coacervate via freeze-thaw treatment of coacervates coated by liposome particles, including liposome particles with heterogenous lamellarity, resulting in coacervate-supported monodisperse giant unilamellar vesicles with gated permeability to polar molecules and remarkable structural and functional stability at extreme environments. This work provides an integrative approach to process crude building blocks towards disciplined and integrated cellular systems, which might have mediated the transition from the inanimate to life. This approach is promisingly utilized for high throughput screening of possible integrated form of primitive life from a high diversity of inanimate matter as well as on demand bulk-generation of monodisperse hierarchical microdroplets with flexibly integrated functions.

Competing Interest Statement

The authors have declared no competing interest.

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Posted February 19, 2021.
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Combinatorial engineering of bulk-assembled monodisperse coacervate droplets towards logically integrated protocells
Qingchuan Li, Qingchun Song, Jing Wei, Yang Cao, Dairong Chen, Ho Cheung Shum
bioRxiv 2021.02.19.432011; doi: https://doi.org/10.1101/2021.02.19.432011
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Combinatorial engineering of bulk-assembled monodisperse coacervate droplets towards logically integrated protocells
Qingchuan Li, Qingchun Song, Jing Wei, Yang Cao, Dairong Chen, Ho Cheung Shum
bioRxiv 2021.02.19.432011; doi: https://doi.org/10.1101/2021.02.19.432011

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