Particuology
·
2025
·
IF 4.3
Shuyu Li,Di Wu,Hui Yu,Xin Huang,Na Wang,Ting Wang,Hongxun Hao
In this work, API nanoscale drugs loaded onto solid lipid microspheres (ND@SLMs) were successfully prepared by combining in-situ crystallization technology and liquid-liquid phase separation (LLPS). This method is characterized by its low energy consumption and the absence of a requirement for high concentrations of surfactants. Tristearin (SSS) was used as the drug carriers, and fenofibrate (FEN) was used as API to verify the feasibility of this method. Characterization was performed using SEM, PXRD, and DSC, while in-situ Raman and EasyViewer enabled real-time monitoring of the particle formation process. The results show that the obtained Active Pharmaceutical Ingredient (API) nanoscale crystals exhibited uniform distribution in the solid lipid carrier and enhanced release rates compared to the bulk ingredients. API droplets prepared by LLPS adhered to the surface of the FEN + SSS droplets played the role of dispersant. Response surface analysis was employed to analyze the independent variables and their interactions, and the optimum value of the processing parameters was obtained. Finally, the expandability of this method to other hydrophobic drugs was verified by ibuprofen (IBU).
研究领域:
药剂学
·
药物递送系统
·
材料科学
·
纳米技术
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产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Wan-Yi Ge,Wen-Pu Shi,Xue-Ting Wang,Huan Liang,Xu-Dong Deng,Liang-Liang Chen,Xiao-Qian Jin,Wei-Hong Guo,Da-Chuan Yin
Protein liquid–liquid phase separation (LLPS) is a significant process in biology and material sciences. Finding suitable conditions for protein LLPS is essential for its in-depth and systematic study. Here, we provide a mixed solution screening kit based on biomacromolecule crowding agents to find protein LLPS conditions. The screening kit consists of 96 chemical formulations, in which the biomacromolecule crowding agents are used as the key components. The aqueous solution of the target protein is mixed with each chemical agent in the kit and then placed in an incubator for some time. The LLPS conditions for the target protein can be found by examining the LLPS phenomena in the droplets. We used nine proteins as model target proteins—lysozyme, bovine serum albumin, bovine hemoglobin, ovalbumin, catalase, FUS, Aβ, Tau, and α-Synuclein—to evaluate the performance of the screening kit. We found that utilization of the screening kit is efficient and useful to find different conditions for LLPS of proteins. The screening results reveal two types of conditions: those that promote and those that inhibit LLPS. Both conditions are extremely valuable because those that promote LLPS can be used to do extensive studies on the LLPS processes of the proteins of interest, whereas those that inhibit LLPS can be utilized as leads for developing novel medications to treat LLPS-related disorders. Furthermore, novel applications for the kit were investigated by utilizing the screening products.
研究领域:
生物学
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材料科学
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生物物理学
·
药学
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DOI
高影响因子
Cell Reports
·
2023
·
IF 8.8
Kaiming Cao,Shixuan Li,Yu Wang,Hongze Hu,Sijia Xiang,Qianling Zhang,Yangzhong Liu
Bacterial cells were long thought to be "bags of enzymes" with minimal internal structures. In recent years, membrane-less organelles formed by liquid-liquid phase separation (LLPS) of proteins or nucleic acids have been found to be involved in many important biological processes, although most of them were studied on eukaryotic cells. Here, we report that NikR, a bacterial nickel-responsive regulatory protein, exhibits LLPS both in solution and inside cells. Analyses of cellular nickel uptake and cell growth of E. coli confirm that LLPS enhances the regulatory function of NikR, while disruption of LLPS in cells promotes the expression of nickel transporter (nik) genes, which are negatively regulated by NikR. Mechanistic study shows that Ni(II) ions induces the accumulation of nik promoter DNA into the condensates formed by NikR. This result suggests that the formation of membrane-less compartments can be a regulatory mechanism of metal transporter proteins in bacterial cells.
研究领域:
微生物学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Cell Reports
·
2025
·
IF 6.9
Sijia Xiang,Zhuanghao Hou,Yu Wang,Yang Yang,Hongze Hu,Chang Yin,Guangming Huang,Kaiming Cao,Yangzhong Liu
Liquid-liquid phase separation (LLPS) of biomolecules is a crucial mechanism in regulating cellular functions through dynamic formation of membrane-less organelles. The assembly of nucleation seeds is a key step that triggers LLPS; however, it is challenging to precisely study its assembly mechanism due to the complexity of the condensation process. Recently, metal ions have been found to play important roles in inducing LLPS. To elucidate the assembling mechanism, a small ubiquitin-like modifier (SUMO) protein was employed as a model protein to study metal-induced condensation. The results indicate that SUMO possesses two weak Cu(II)-binding sites across the protein surface, enabling intermolecular bridging among SUMO molecules. The formation of assembling seeds is confirmed by mass photometry analysis, showing the Cu(II)-induced dynamic clusterization of SUMO at nanoscale. Increasing the Cu(II) binding affinity of SUMO significantly promotes the protein condensation, underscoring the pivotal role of Cu(II) coordination in LLPS. This work provides insights into the protein assembly mechanism through non-specific intermolecular metal coordination.
研究领域:
生物物理学
·
分子生物学
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生物化学
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结构生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Kaijie Qian,Lorenzo Stella,Fanjun Liu,David S. Jones,Gavin P. Andrews,Yiwei Tian
Understanding the interplay between kinetics and thermodynamics of polymer-mediated liquid–liquid phase separation is crucial for designing and implementing an amorphous solid dispersion formulation strategy for poorly water-soluble drugs. This work investigates the phase behaviors of a poorly water-soluble model drug, celecoxib (CXB), in a supersaturated aqueous solution with and without polymeric additives (PVP, PVPVA, HPMCAS, and HPMCP). Drug–polymer–water ternary phase diagrams were also constructed to estimate the thermodynamic behaviors of the mixtures at room temperature. The liquid–liquid phase separation onset point for CXB was detected using an inline UV/vis spectrometer equipped with a fiber optic probe. Varying CXB concentrations were achieved using an accurate syringe pump throughout this study. The appearance of the transient nanodroplets was verified by cryo-EM and total internal reflection fluoresence microscopic techniques. The impacts of various factors, such as polymer composition, drug stock solution pumping rates, and the types of drug–polymer interactions, are tested against the onset points of the CXB liquid–liquid phase separation (LLPS). It was found that the types of drug–polymer interactions, i.e., hydrogen bonding and hydrophobic interactions, are vital to the position and shapes of LLPS in the supersaturation drug solution. A relation between the behaviors of LLPS and its location in the CXB–polymer–water ternary phase diagram was drawn from the findings.
研究领域:
药学
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材料科学
·
化学工程
·
生物物理学
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DOI
PubMed
高影响因子
JOURNAL OF POLYMER RESEARCH
·
2021
·Vol. 28
·期 8
·1-10
·
IF 3.097
Yang Bin,Wang Shu-Qing,Chen Qing-Ting,Ding Meng-Ya,Yu Yang-Nan,Pan Yang,Xia Ru,Ge Qian-Qian,Miao Ji-Bin,Qian Jia-Sheng,Chen Peng,Shi You,Tu You-Lei
Thermally-induced phase separation (TIPS) was used to fabricate polyvinylidene fluoride (PVDF) films under different quenching conditions. Temperature gradient fields were in-situ formed inside the films through varying the TIPS quenching temperature, and an enthalpy transformation method (ETM) was adopted to simulate the temperature gradient fields during the TIPS process. Our findings showed that there existed liquid–liquid phase separation (LLPS) even at higher PVDF concentration (e.g., above the monotectic point). The coexistence and competition between liquid–liquid and solid–liquid phase separations were significantly determined by the cooling rate, which helped to explain the formation mechanisms of hierarchical morphologies observed in the final TIPS films. The present work will be of substantial importance to further studies on an industrial tuning of the microstructure and performance of TIPS films through the operational parameter control.
研究领域:
材料科学
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高分子工程
·
相变研究
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DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Jian Liu,Junbo Li,Yan Huang,Tong Li,Cheng Xu,Zhengyu Tao,Wei Ji,Xin Huang
Biomolecular condensates formed by liquid–liquid phase separation (LLPS) play a crucial role in organizing biochemical processes within living cells. The phase transition of these condensates from a functional liquid-like state to a pathological gel-like or solid-like state is believed to be linked to cellular dysfunction and various diseases. Here, we present a biomimetic model to demonstrate that endogenous enzyme-catalyzed crosslinking within condensate-mimicked coacervate microdroplets can promote a liquid-to-gel phase transition. We identify the transformation in physical characteristics of the densely packed microdroplets including reduced internal mobility, increased storage modulus, selective blocking of large nanoparticles, and enhanced salt resistance. The reversible dynamics of gel-like microdroplets mediated by ionic strength exhibited a limited release and recapture of sequestered positively charged guest molecules. Furthermore, we validate that the phase transition contributes to a restricted biochemical process through an enzymatic cascade. Overall, this work represents an adaptive in vitro platform for exploring the phase transitions associated with the physiological functions of biomolecular condensates and offers chemical insights and perspectives for investigating potential mechanisms involved in phase transitions.
研究领域:
生物物理
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生物化学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULES
·
2021
·
IF 5.985
Ye Wang,Chao Li,Lei Ma,Xiyu Wang,Kai Wang,Xinhua Lu,Yuanli Cai
Development of spatially restricted liquid–liquid phase separation (LLPS) systems emulating biomolecular condensates is a major challenge in coacervating materials science, due to lack of approaches for spatially restricted coacervation of sequence-defined zwitterionic segments resembling intrinsically disordered proteins. Herein, we present interfacial LLPS-driven polymerization-induced electrostatic self-assembly, namely, interfacial LLPS-PIESA. The asymmetric charge sequence patterning of zwitterionic growing segments is achieved via spontaneous polymerization of ion-pair monomers within a nanoparticle core–shell interface. We show that charge sequence can profoundly affect the self-coacervation, leading to droplet dispersions, dense coacervates, and free-standing hydrogels. Moreover, the interfacial LLPS-PIESA shows a programmed hierarchical condensation self-assembly mechanism involving vesicles-to-lamellae transition, interfacial self-coacervation, lamellae-to-sheets transition, layer-by-layer sheet self-assembly, spatially restricted condensation and agglomeration, and redispersing into fibril network condensates under dynamic evolving surface charge regulation. The spatially restricted asymmetric charge sequence patterning, interfacial self-coacervation, and programmed hierarchical condensation self-assembly, all these elements can serve as the primary principles for the asymmetric charge sequence patterning design of hierarchically nanostructured condensates that emulate cellular biomolecular condensates.
研究领域:
材料科学
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聚合物化学
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软物质物理
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生物物理学
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DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Li Xi,Yu Linwei,Liu Xikai,Shi Tianyi,Zhang Yu,Xiao Yushuo,Wang Chen,Song Liangliang,Li Ning,Liu Xinran,Chen Yuchen,Petersen Robert B.,Cheng Xiang,Xue Weikang,Yu Yanxun V.,Xu Li,Zheng Ling,Chen Hong,Huang Kun
Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.
研究领域:
神经科学
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分子生物学
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细胞生物学
·
神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2025
·Vol. 122
·期 13
·e2419507122
·
IF 9.1
Vincent Mukwaya,Xiaolei Yu,Shuo Yang,Stephen Mann,Hongjing Dou
Liquid–liquid phase separation (LLPS) has been achieved in various cytomimetic (protocell) models, but controlling molecular condensation using noninert crowders to systematically alter protocell function remains challenging. Intracellular ATP levels influence protein–protein interactions, and dysregulation of ATP can alter cellular crowding dynamics, thereby disrupting the normal formation or dissolution of condensates. Here, we develop a membranized protocell model capable of endogenous LLPS and liquid–gel-like phase separation through precise manipulation of intermolecular interactions within semipermeable polysaccharide-based microcapsules (polysaccharidosomes, P-somes), prepared using microtemplate-guided assembly. We demonstrate that intraprotocellular diffusion-mediated LLPS can be extended into the liquid–gel-like domain by the uptake of the biologically active crowder ATP, resulting in a range of modalities dependent on the fine-tuning of molecular condensation. Endogenous enzyme activity in these crowded polysaccharidosomes is enhanced compared to free enzymes in solution, though this enhancement diminishes at higher levels of intraprotocellular condensation. Additionally, increased molecular crowding inhibits intraprotocell DNA strand displacement reactions. Our findings introduce an expedient and optimized approach to the batch construction of membranized protocell models with controllable molecular crowding and functional diversity. Our mix–incubate–wash protocol for inducing endogenous LLPS in membranized protocells offers potential applications in microreactor technology, environmental sensing, and the delivery and sustained release of therapeutics.
研究领域:
生物物理学
·
合成生物学
·
化学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULES
·
2024
·
IF 5.1
Ying Cao,Ran Zhang,Xiaoyue Xu,Xiyu Wang,Yuting Li,Xinhua Lu,Yuanli Cai
Biomimetic synthesis represents a cutting-edge topic in chemical and materials sciences. Herein, we present an approach to bioinspired polymerization autocatalysis using a single amino acid monomer in water. Similar to biomolecular condensates, this monomer undergoes an entropically driven liquid–liquid phase separation (LLPS)-mode self-assembly involving densely charged molecular clusters formation, LLPS of charged monomer clusters leading to submicron-scale droplets, crystallization of charged monomer clusters within droplet crowding environments resulting in dynamic nanocrystals@droplets and finally less dynamic aged-lamellae. Supramolecular chirality inversion and nanocrystal disassembly into charged monomer clusters occur upon doping of a minor RAFT agent. Autocatalysis with solvent-tuned H+-feedback and covalent-driven chirality inversion is achieved using extremely dynamic nanocrystals@droplets. Decelerated kinetics upon deionization/ion-pairing underscore the vital importance of LLPS for the “higher charge repulsion leads to more rapid polymerization”, yielding polymer nanoparticles with protein-like structural complexity up to >98% conversion in 2-min-propagation period. This autocatalysis provides new insights into bioinspired efficient synthesis of polymer nanoparticles.
研究领域:
化学科学
·
材料科学
·
聚合物化学
·
纳米技术
·
生物物理学
✓ 已验证
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Jia Liu,Liuting Zheng,Xinyue Li,Wei Tang,Manyu Guo,Yuxing Wang,Xiaoqi Tan,Jiajia Chang,Huiyue Zhao,Dongsheng Zhu,Yu-qiang Ma,Da Huo
Understanding the interaction between nanomaterials and cellular structures is crucial for nanoparticle applications in biomedicine. We have identified a subtype of stress granules, called nanomaterial-provoked stress granules (NSGs), induced by gold nanorods (AuNRs). These NSGs differ from traditional SGs in their physical properties and biological functions. Uptake of AuNRs causes reactive oxygen species accumulation and protein misfolding in the cell, leading to NSG formation. Physically, NSGs have a gel-like core and a liquid-like shell, influenced positively by HSP70 and negatively by HSP90 and the ubiquitin-proteasome system. AuNRs promote NSG assembly by interacting with G3BP1, reducing the energy needed for liquid–liquid phase separation (LLPS). NSGs impact cellular functions by affecting mRNA surveillance and activating Adenosine 5′-monophosphate (AMP)-activated protein kinase signaling, crucial for a cellular stress response. Our study highlights the role of LLPS in nanomaterial metabolism and suggests NSGs as potential targets for drug delivery strategies, advancing the field of nanomedicine.
研究领域:
纳米生物技术
·
细胞生物学
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）