Mechanisms of prebiotic compartmentalization are central to providing insights into how protocellular systems emerged on the early Earth. Protocell models are based predominantly on the membrane self-assembly of fatty-acid vesicles, although membrane-free scenarios that involve liquid-liquid microphase separation (coacervation) have also been considered. Here we integrate these alternative models of prebiotic compartmentalization and develop a hybrid protocell model based on the spontaneous self-assembly of a continuous fatty-acid membrane at the surface of preformed coacervate microdroplets prepared from cationic peptides/polyelectrolytes and adenosine triphosphate or oligo/polyribonucleotides. We show that the coacervate-supported membrane is multilamellar, and mediates the selective uptake or exclusion of small and large molecules. The coacervate interior can be disassembled without loss of membrane integrity, and fusion and growth of the hybrid protocells can be induced under conditions of high ionic strength. Our results highlight how notions of membrane-mediated compartmentalization, chemical enrichment and internalized structuration can be integrated in protocell models via simple chemical and physical processes.
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http://dx.doi.org/10.1038/nchem.1921 | DOI Listing |
J Am Chem Soc
January 2025
Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR 99999, China.
A low-molecular-weight compound whose structure strikes a fine balance between hydrophobicity and hydrophilicity may form coacervates via liquid-liquid phase separation in an aqueous solution. These coacervates may encapsulate and convoy proteins across the plasma membrane into the cell. However, releasing the cargo from the vehicle to the cytosol is challenging.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, China.
The spontaneous emergence of lipid vesicles in the absence of evolved biological machinery represents a major challenge for bottom-up synthetic biology. We show that coacervate microdroplets could create a compartmentalized environment that enriches lipid molecules and facilitates their spontaneous assembly into lipid vesicles. These vesicles can escape from the coacervate microdroplets in a continuous process under non-equilibrium conditions, resembling a constant production process akin to a "primitive enzyme" factory assembly line.
View Article and Find Full Text PDFNat Commun
November 2024
Center for Sustainable Materials (SusMat), School of Materials Science and Engineering, Nanyang Technological University, 639798, Singapore, Singapore.
Phase-separating peptides (PSPs) self-assembling into coacervate microdroplets (CMs) are a promising class of intracellular delivery vehicles that can release macromolecular modalities deployed in a wide range of therapeutic treatments. However, the molecular grammar governing intracellular uptake and release kinetics of CMs remains elusive. Here, we systematically manipulate the sequence of PSPs to unravel the relationships between their molecular structure, the physical properties of the resulting CMs, and their delivery efficacy.
View Article and Find Full Text PDFChem Commun (Camb)
November 2024
Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory of Polymer Physics and Chemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Coacervate microdroplets, arising from liquid-liquid phase separation, have emerged as promising models for primary cells, demonstrating the ability to regulate biomolecular enrichment, create chemical gradients, accelerate confined reactions, and even express proteins. Notably, multiphase coacervation provides a robust framework to replicate hierarchically complex cellular structures, offering valuable insights into cellular organization and function. In this review, we explore the recent advancements in the study of multiphase coacervates, focusing on design strategies, underlying mechanisms, structural control, and their applications in biomimetics.
View Article and Find Full Text PDFInt J Biol Macromol
November 2024
Jihua Institute of Biomedical Engineering and Technology, Jihua Laboratory, Foshan 528000, People's Republic of China. Electronic address:
A water-in-water (W/W) emulsion consists of microdroplets was formed by the spontaneous liquid-liquid separation by mixing polyacrylic acid and chitosan oligosaccharide in water, and these microdropletes were stabilized by nano-chitin, formed water-in-water Pickering emulsions. By taking the advantage of interfacial adsorption of nano-chitin, the W/W emulsion droplets composed of polyacrylic acid/chitosan oligosaccharide (COS/PAA) polyelectrolyte coacervate were successfully stabilized. Research results indicated that composite microspheres were formed by the nano-chitin stabilized COS/PAA emulsion, and the size of these composite microspheres was related to the concentration and morphology of the nano-chitin.
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