Membranized Coacervate Microdroplets: from Versatile Protocell Models to Cytomimetic Materials

Accounts of Chemical Research, Год журнала: 2023, Номер 56(3), С. 297 - 307

Опубликована: Янв. 10, 2023

ConspectusAlthough complex coacervate microdroplets derived from associative phase separation of counter-charged electrolytes have emerged as a broad platform for the bottom-up construction membraneless, molecularly crowded protocells, absence an enclosing membrane limits more sophisticated artificial cells and their use functional cytomimetic materials. To address this problem, we others recently developed chemical-based strategies membranization preformed microdroplets. In Account, review our recent work on diverse systems using range building blocks assembly processes. First, briefly introduce unusual nature coacervate/water interface, emphasizing ultralow interfacial tension width physiochemical properties that require special attention in judicious design membranized Second, classify into two different approaches: (i) self-assembly by surface-active such molecular amphiphiles (fatty acids, phospholipids, block copolymers, protein–polymer conjugates) or nano- microscale objects (liposomes, nanoparticle surfactants, cell fragments, living cells) with appropriate wettability; (ii) droplet-to-vesicle reconfiguration employing auxiliary surface reconstruction agents triggering endogenous transitions (self-membranization) under nonstoichiometric (charge mismatched) conditions. We then discuss key behaviors coacervate-based model protocells. Customizable permeability is achieved synergistic effects operating between interior surrounding membrane. contrast, metabolic-like reactivity, diffusive chemical signaling, collective operations occur specifically protocell networks comprising populations each case, these can give rise to materials capable promising cell-like applications. For example, immobilizing spatially segregated enzyme-loaded phospholipid-coated protocells concentrically tubular hydrogels delivers prototissue-like bulk generate nitric oxide vitro, enabling platelet deactivation inhibition blood clot formation. Alternatively, therapeutic vivo vasoactivity, high hemocompatibility, increased circulation times are constructed spontaneous hemoglobin-containing cell-membrane fragments Higher-order endocytosis nanoparticle-caged hosts selectively actively capture guest responses exogenous stimuli via enzyme-mediated reactions. Finally, current limitations programming microdroplets, which may help guide future directions emerging research area. Taken together, hope Account will inspire new advances promote application development integrated models

Язык: Английский

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Coacervate Droplets for Synthetic Cells

Small Methods, Год журнала: 2023, Номер 7(12)

Опубликована: Июль 18, 2023

Abstract The design and construction of synthetic cells – human‐made microcompartments that mimic features living have experienced a real boom in the past decade. While many efforts been geared toward assembling membrane‐bounded compartments, coacervate droplets produced by liquid–liquid phase separation emerged as an alternative membrane‐free compartmentalization paradigm. Here, dual role cell research is discussed: encapsulated within membrane‐enclosed coacervates act surrogates membraneless organelles ubiquitously found cells; alternatively, they can be viewed crowded cytosol‐like chassis for constructing integrated cells. After introducing key concepts coacervation illustrating chemical diversity systems, their physicochemical properties resulting bioinspired functions are emphasized. Moving from suspensions free floating coacervates, two nascent roles these highlighted: organelle‐like modules templates. Building discussion on recent studies literature, potential to assemble capable multiple life‐inspired showcased. Future challenges still tackled field finally discussed.

Язык: Английский

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Superstructural ordering in self-sorting coacervate-based protocell networks

Nature Chemistry, Год журнала: 2023, Номер 16(2), С. 158 - 167

Опубликована: Ноя. 6, 2023

Язык: Английский

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Plant Cell-Inspired Membranization of Coacervate Protocells with a Structured Polysaccharide Layer

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(23), С. 12576 - 12585

Опубликована: Июнь 2, 2023

The design of compartmentalized colloids that exhibit biomimetic properties is providing model systems for developing synthetic cell-like entities (protocells). Inspired by the cell walls in plant cells, we developed a method to prepare membranized coacervates as protocell models coating membraneless liquid-like microdroplets with protective layer rigid polysaccharides. Membranization not only endowed colloidal stability and prevented aggregation coalescence but also facilitated selective biomolecule sequestration chemical exchange across membrane. polysaccharide wall surrounding coacervate protocells acted stimuli-responsive structural barrier enabled enzyme-triggered membrane lysis initiate internalization killing Escherichia coli. were capable spatial organization into structured tissue-like assemblages, offering means mimic metabolism cell-to-cell communication. We envision surface engineering this work generates platform constructing advanced mimetics sophisticated behaviors.

Язык: Английский

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Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes

Advanced Materials, Год журнала: 2024, Номер 36(26)

Опубликована: Апрель 7, 2024

Abstract Brain disorders represent a significant challenge in medical science due to the formidable blood–brain barrier (BBB), which severely limits penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into innovative realm biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential circumvent BBB's restrictions. By mimicking native properties, these nanocarriers emerge as promising solution for enhancing drug delivery brain, offering strategic advantage overcoming barrier's selective permeability. The unique benefits leveraging membranes from various sources is evaluated advanced technologies fabricating membrane‐encapsulated nanoparticles capable masquerading endogenous cells are examined. enables targeted broad spectrum therapeutic agents, ranging small molecule drugs proteins, thereby providing an approach neurocare. Further, contrasts capabilities limitations with traditional methods, underlining enable targeted, sustained, minimally invasive modalities. concluded perspective on clinical translation underscoring transformative impact landscape intractable brain diseases.

Язык: Английский

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Self-assembly of stabilized droplets from liquid–liquid phase separation for higher-order structures and functions

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Апрель 9, 2024

Dynamic microscale droplets produced by liquid-liquid phase separation (LLPS) have emerged as appealing biomaterials due to their remarkable features. However, the instability of limits construction population-level structures with collective behaviors. Here we first provide a brief background in context materials properties. Subsequently, discuss current strategies for stabilizing including physical and chemical modulation. We also recent development LLPS various applications such synthetic cells biomedical materials. Finally, give insights on how stabilized can self-assemble into higher-order displaying coordinated functions fully exploit potentials bottom-up biology applications.

Язык: Английский

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Peptide-Mediated Liquid-Liquid Phase Separation and Biomolecular Condensates

Soft Matter, Год журнала: 2025, Номер 21(10), С. 1781 - 1812

Опубликована: Янв. 1, 2025

Peptide-mediated liquid–liquid phase separation (LLPS) underpins the formation of dynamic biomolecular condensates, regulated by diverse molecular interactions, and highlights potential applications in drug delivery synthetic biology.

Язык: Английский

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Binary peptide coacervates as an active model for biomolecular condensates

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 11, 2025

Abstract Biomolecular condensates formed by proteins and nucleic acids are critical for cellular processes. Macromolecule-based coacervate droplets liquid-liquid phase separation serve as synthetic analogues, but limited complex compositions high molecular weights. Recently, short peptides have emerged an alternative component of coacervates, tend to form metastable microdroplets that evolve into rigid nanostructures. Here we present programmable coacervates using binary mixtures diphenylalanine-based peptides. We show the presence different stabilizes prevents formation structures, allowing peptide be used stable adaptive compartments. This approach allows fine control droplet dynamic morphological changes in response physiological triggers. As compartments, sequester hydrophobic molecules enhance bio-orthogonal catalysis. In addition, incorporation model cells enables design Boolean logic gates. Our findings highlight potential creating biomimetic systems provide insight principles biomolecular condensates.

Язык: Английский

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Signal processing and generation of bioactive nitric oxide in a model prototissue

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Сен. 6, 2022

The design and construction of synthetic prototissues from integrated assemblies artificial protocells is an important challenge for biology bioengineering. Here we spatially segregate chemically communicating populations enzyme-decorated phospholipid-enveloped polymer/DNA coacervate in hydrogel modules to construct a tubular prototissue-like vessel capable modulating the output bioactive nitric oxide (NO). By decorating with glucose oxidase, horseradish peroxidase or catalase arranging different concentrically, glucose/hydroxyurea dual input leads logic-gate signal processing under reaction-diffusion conditions, which results distinct NO internal lumen model prototissue. exploited inhibit platelet activation blood clot formation samples plasma whole located channel device, thereby demonstrating proof-of-concept use anticoagulation applications. Our highlight opportunities development organized prototissue assemblages provide step towards organization biochemical processes micro-compartmentalized media, micro-reactor technology soft functional materials.

Язык: Английский

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Continuous Transformation from Membrane‐less Coacervates to Membranized Coacervates and Giant Vesicles: toward Multicompartmental Protocells with Complex (Membrane) Architectures

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(34)

Опубликована: Июнь 7, 2024

The membranization of membrane-less coacervates paves the way for exploitation complex protocells with regard to structural and cell-like functional behaviors. However, controlled transformation from membranized vesicles remains a challenge. This can provide stable (multi)phase (multi)compartmental architectures through reconfiguration coacervate droplets in presence (bioactive) polymers, bio(macro)molecules and/or nanoobjects. Herein, we present continuous protocell and, ultimately, giant hybrid vesicles. process is orchestrated by altering balance non-covalent interactions varying concentrations an anionic terpolymer, leading dynamic processes such as spontaneous terpolymer nanoparticles at surface, disassembly phase mediated excess charge, redistribution components membrane. diverse during course distinct features molecular permeability. Notably, introduction multiphase this signifies advancements toward creation synthetic cells different diffusible compartments. Our findings emphasize highly reorganization represents novel step development advanced sophisticated more precise compositions (membrane) structures.

Язык: Английский

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