A Single Amino Acid Model for Hydrophobically Driven Liquid–Liquid Phase Separation DOI
Heung Bae Jeon, Joo Hyung Lee,

A.J. Park

et al.

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

This study proposes fluorenylmethoxycarbonyl (Fmoc)-protected single amino acids (Fmoc-AAs) as a minimalistic model system to investigate liquid-liquid phase separation (LLPS) and the elusive liquid-to-solid transition of condensates. We demonstrated that Fmoc-AAs exhibit LLPS depending on pH ionic strength, primarily driven by hydrophobic interactions. Systematic examination conditions under which each Fmoc-AA undergoes revealed distinct residue-dependent trends in critical concentrations behavior. Importantly, we elucidated process, suggesting it may be molecular mechanism different from LLPS. condensates showed promise for biomolecular enrichment catalytic applications. work provides significant insights into mechanisms subsequent transition, offering robust platform future studies related protocells protein aggregation diseases.

Language: Английский

Membranized Coacervate Microdroplets: from Versatile Protocell Models to Cytomimetic Materials DOI Creative Commons
Ning Gao, Stephen Mann

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(3), P. 297 - 307

Published: Jan. 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

Language: Английский

Citations

81
Coacervate Droplets for Synthetic Cells DOI Creative Commons

Zi Lin,

Thomas Beneyton, Jean‐Christophe Baret

et al.

Small Methods, Journal Year: 2023, Volume and Issue: 7(12)

Published: July 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.

Language: Английский

Citations

49
Superstructural ordering in self-sorting coacervate-based protocell networks DOI
Wenjing Mu, Liyan Jia, Musen Zhou

et al.

Nature Chemistry, Journal Year: 2023, Volume and Issue: 16(2), P. 158 - 167

Published: Nov. 6, 2023

Language: Английский

Citations

45
Plant Cell-Inspired Membranization of Coacervate Protocells with a Structured Polysaccharide Layer DOI
Yanglimin Ji, Yiyang Lin, Yan Qiao

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(23), P. 12576 - 12585

Published: June 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.

Language: Английский

Citations

43
Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes DOI
Jun Liao, Lidong Gong,

Qingqiang Xu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)

Published: April 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.

Language: Английский

Citations

30
Self-assembly of stabilized droplets from liquid–liquid phase separation for higher-order structures and functions DOI Creative Commons
Mehwish Naz,

Lin Zhang,

Chong Chen

et al.

Communications Chemistry, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 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.

Language: Английский

Citations

17
Signal processing and generation of bioactive nitric oxide in a model prototissue DOI Creative Commons
Songyang Liu, Yanwen Zhang, Xiaoxiao He

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 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.

Language: Английский

Citations

45
Interfacial energy-mediated bulk transport across artificial cell membranes DOI
Jiaqi Tian,

Mu-Yueh Chang,

Chen Chen

et al.

Nature Chemical Engineering, Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Language: Английский

Citations

9
Binary peptide coacervates as an active model for biomolecular condensates DOI Creative Commons
Shoupeng Cao, Peng Zhou, Guizhi Shen

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 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.

Language: Английский

Citations

1
Coacervate Microdroplets as Synthetic Protocells for Cell Mimicking and Signaling Communications DOI
Zefeng Wang, Min Zhang, Yan Zhou

et al.

Small Methods, Journal Year: 2023, Volume and Issue: 7(12)

Published: March 12, 2023

Synthetic protocells are minimal systems that mimic certain properties of natural cells and used to research the emergence life from a nonliving chemical network. Currently, coacervate microdroplets, which formed via liquid-liquid phase separation, receiving wide attention in context cell biology protocell research; these microdroplets notable because they can provide liquid-like compartment structures for biochemical reactions by creating highly macromolecular crowded local environments. In this review, an overview recent on formation through separation; design coacervate-based stimuli-responsive protocells, multichamber membranized protocells; their behaviors, is provided. The simplified models with precisely defined tunable compositions advance understanding requirements cellular structure function. Efforts then discussed establish signal communication consortia, as fundamental feature coordinates matter exchanges energy fluxes dynamically space time. Finally, some perspectives challenges future developments synthetic biomimetic science biomedical applications

Language: Английский

Citations

19