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Impact of α-tocopherol derivatives on the structural and functional properties of model lipid nanocarriers: A biophysical modeling study α-生育酚衍生物对模型脂质纳米载体结构和功能特性的影响:生物物理建模研究。
IF 2.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-15 DOI: 10.1016/j.chemphyslip.2025.105539
Anita Dudek , Maciej Spiegel , Dominika Benkowska-Biernacka , Magdalena Domańska , Hanna Pruchnik
While α-tocopherol is widely studied for its antioxidant role in membranes, its potential as a functional component of liposomal carriers remains underexplored, despite their range of interesting biological activities and growing use in nanocarrier systems. This study systematically evaluates how three tocopherol derivatives - α-tocopherol phosphate (TP), α-tocopherol succinate (TS), and α-tocopherol polyethylene glycol succinate (TPGS)—affect nanoliposomes, focusing on colloidal stability, encapsulation efficiency, and fundamental membrane properties such as fluidity, hydration, and thermotropic behavior. Results showed that all α-tocopherol derivatives significantly altered membrane properties, inducing structural changes in both the lipid chain and polar regions of the liposome bilayer. TS enhanced membrane rigidity and reduced permeability, while TP increased fluidity and promoted payload release. TPGS, with its bulky PEG chain, stabilized liposomes but induced phase heterogeneity. Additionally, all derivatives lowered the lipid main phase transition temperature and altered its thermotropic behavior. Despite these disruptions, the derivatives preserved nanoscale vesicle sizes (∼100 nm) and monodisperse distributions (PDI < 0.3) over extended storage. These experimental observations were further supported by molecular dynamics simulations, which confirmed differences in membrane affinity among the derivatives, with TS showing the strongest binding affinity. The simulations also revealed that the derivatives' positioning within the bilayer and their interactions—mainly hydrogen bonding and hydrophobic contacts—contribute to their distinct effects on membrane structure and dynamics. Collectively, these findings demonstrate that α-tocopherol derivatives distinctly modulate liposomal membrane architecture and behavior in a structure-dependent manner, offering promising tools for tuning nanocarrier performance in pharmaceutical applications.
虽然α-生育酚因其在膜中的抗氧化作用而被广泛研究,但其作为脂质体载体的功能成分的潜力仍未得到充分开发,尽管它们具有一系列有趣的生物活性,并且在纳米载体系统中的应用越来越广泛。本研究系统评估了三种生育酚衍生物α-生育酚磷酸(TP)、α-生育酚琥珀酸酯(TS)和α-生育酚聚乙二醇琥珀酸酯(TPGS)对纳米脂质体的影响,重点研究了胶体稳定性、包封效率和基本的膜性质,如流动性、水合性和热致性。结果表明,所有α-生育酚衍生物均能显著改变膜的性质,引起脂质体双分子层脂链和极性区域的结构变化。TS增强了膜的刚性,降低了渗透率,而TP增加了流动性,促进了有效载荷的释放。由于其庞大的PEG链,TPGS稳定了脂质体,但引起了相异质性。此外,所有衍生物均降低了脂质主相变温度,改变了其热致性。尽管存在这些破坏,衍生物在延长的存储时间内保持了纳米级囊泡大小(~100nm)和单分散分布(PDI < 0.3)。这些实验结果得到了分子动力学模拟的进一步支持,证实了不同衍生物的膜亲和性差异,其中TS表现出最强的结合亲和性。模拟还表明,衍生物在双层中的位置及其相互作用(主要是氢键和疏水接触)有助于它们对膜结构和动力学的不同影响。总的来说,这些发现表明α-生育酚衍生物以结构依赖的方式明显调节脂质体膜的结构和行为,为调整纳米载体在制药应用中的性能提供了有前途的工具。
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引用次数: 0
Raman spectroscopy characterization of interbilayer water of hydrated phospholipid multibilayers 水合磷脂多层膜层间水的拉曼光谱表征
IF 2.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-30 DOI: 10.1016/j.chemphyslip.2025.105529
E.A. Dobrynina, S.V. Adichtchev, N.V. Surovtsev
The properties of phospholipid bilayers, which are important in various biophysical and biomedical studies, critically depend on the hydration of the lipid bilayer. Interbilayer water in multilamellar vesicles or planar multilayers is a very convenient object for studying the interfacial lipid-water interaction. However, many parameters of the interbilayer water remain incompletely studied, and in some cases different experimental methods yield different parameters of interbilayer water. Here, we developed a Raman spectroscopy method for characterizing interbilayer water in multilayer phospholipid samples. This method was applied to one saturated (DPPC) and one unsaturated (DOPC) phospholipid hydrated at high relative humidity and studied over a wide temperature range. It was found that although above the freezing point of water the OH stretching spectra of interbilayer water were similar to those of bulk water, only about one-fifth of the interbilayer water crystallized at the lowest experimental temperature (110 K). In combination with Raman spectra of aqueous suspensions of phospholipids of known compositions, the number of interbilayer H2O molecules per lipid molecule (hydration number) was determined. The hydration number was found for the ordered (gel) and disordered (fluid) phases of hydrated phospholipid bilayers at different temperatures and several relative humidities. The results were compared with values of the hydration number obtained by other methods, and an interpretation was proposed that takes into account the fractions of the free and non-free (perturbed) interbilayer water.
磷脂双分子层的性质在各种生物物理和生物医学研究中都很重要,它的性质很大程度上取决于脂双分子层的水合作用。多层囊泡或平面多层囊泡中的双层水是研究界面脂水相互作用的一个非常方便的对象。然而,对于双层水的许多参数的研究还不完全,在某些情况下,不同的实验方法会得到不同的双层水参数。在这里,我们开发了一种拉曼光谱方法来表征多层磷脂样品中的双层水。该方法应用于一种饱和磷脂(DPPC)和一种不饱和磷脂(DOPC)在高相对湿度下水合,并在宽温度范围内进行了研究。研究发现,尽管在水的冰点以上,双分子层水的OH拉伸光谱与体水相似,但在最低实验温度(110 K)下,只有约五分之一的双分子层水结晶。结合已知组成的磷脂水悬浮液的拉曼光谱,确定了每个脂质分子的双层间水分子数(水合数)。在不同的温度和不同的相对湿度下,发现了水合磷脂双层的有序相(凝胶相)和无序相(流体相)的水合数。结果与其他方法得到的水化数值进行了比较,并提出了考虑自由和非自由(扰动)双层水的分数的解释。
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引用次数: 0
Bamboo charcoal mitigates oxidised LDL-induced foam cell formation via molecular interaction and adsorption: Evidence from in silico and in vitro studies 竹炭通过分子相互作用和吸附减轻氧化低密度脂蛋白诱导的泡沫细胞形成:来自硅和体外研究的证据
IF 2.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-30 DOI: 10.1016/j.chemphyslip.2025.105528
Mutaman Hussein Abdullah , Ahmad Naqib Shuid , Mohd Yusmaidie Aziz , Muhammad Azrul Zabidi , Muhammad Mahyiddin Ramli , Rafeezul Mohamed
Atherosclerosis is partially driven by the accumulation of oxidised low-density lipoprotein (oxLDL), which facilitates foam cell formation and vascular inflammation. This research examines the efficacy of bamboo charcoal (BC) as a bioactive agent for neutralising oxLDL using both in silico and in vitro methodologies. Molecular docking demonstrated significant binding affinities between BC and essential constituents of oxLDL, such as oxidised cholesterol and apolipoprotein B-100, facilitated by π–π stacking and electrostatic interactions. Molecular dynamics simulations demonstrated the stability of these complexes over 300 ns, indicating sustained molecular interactions. Quantum chemical calculations employing density functional theory showed a narrow HOMO–LUMO gap of 0.45 eV and a significant dipole moment of approximately 45 D, underscoring the reactive and polar characteristics of BC. Electrostatic potential mapping and thermodynamic analyses provided additional evidence for BC's spontaneous and stable binding to oxLDL components. The Oil Red O staining and total cholesterol estimation assays were conducted on oxLDL-treated RAW 264.7 macrophages in vitro indicated that BC significantly decreased macrophage-derived foam cell formation, thereby confirming its ability to reduce oxLDL-induced lipid accumulation. The findings suggest that BC functions as a physical adsorbent and a participant in direct chemical interactions with oxLDL, providing a dual-action therapeutic approach to atherosclerosis.
动脉粥样硬化部分是由氧化低密度脂蛋白(oxLDL)的积累驱动的,它促进泡沫细胞的形成和血管炎症。本研究利用硅中和法和体外法检测了竹炭(BC)作为生物活性剂中和oxLDL的功效。分子对接表明,BC与oxLDL的主要成分(如氧化胆固醇和载脂蛋白B-100)之间存在显著的结合亲和力,这是π -π堆叠和静电相互作用促成的。分子动力学模拟证明了这些配合物在300 ns以上的稳定性,表明持续的分子相互作用。采用密度泛函理论的量子化学计算表明,BC的HOMO-LUMO隙窄,为0.45 eV,偶极矩显著,约为45 D,强调了BC的活性和极性特征。静电电位映射和热力学分析进一步证明了BC与oxLDL组分的自发和稳定结合。体外对氧化低密度脂蛋白处理的RAW 264.7巨噬细胞进行Oil Red O染色和总胆固醇测定表明,BC显著减少巨噬细胞来源的泡沫细胞形成,从而证实了其减少氧化低密度脂蛋白诱导的脂质积累的能力。研究结果表明,BC作为一种物理吸附剂和oxLDL的直接化学相互作用的参与者,为动脉粥样硬化提供了双重作用的治疗方法。
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引用次数: 0
The puzzle of sphingolipids and cholesterol under the atomic force microscope: bilayer thicknesses and breakthrough forces 原子力显微镜下鞘脂和胆固醇之谜:双层厚度和突破力。
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-15 DOI: 10.1016/j.chemphyslip.2025.105527
Aritz B. García-Arribas , Alicia Alonso , Félix M. Goñi
A variety of studies published in the last decades in the field of lipid biophysics deal with the puzzle regarding the relationship between the signaling power of bioactive lipids (sphingolipids) and their capacity to induce lipid membrane heterogeneity (domains). Advances in technology, particularly Atomic Force Microscopy (AFM), have provided a solid contribution in this regard. Moreover, supported planar bilayers (SPB) have become an established membrane model in the study of lipid-lipid interactions. However, in spite of the large amount of published results in this field, the data remain scattered, and a coherent collection that allows easy access to the investigator is missing. This review summarizes the relevant results obtained in our laboratory through the use of AFM under comparable experimental conditions, offering a collection of data on supported lipid bilayer thicknesses and breakthrough forces. An extensive list of lipid compositions including phospholipids, cholesterol and sphingolipids (sphingomyelins, ceramides), at varying molecular ratios, has been considered.
在过去的几十年里,脂质生物物理学领域发表了许多关于生物活性脂质(鞘脂)的信号传导能力与其诱导脂质膜非均质性(结构域)的能力之间关系的研究。技术的进步,特别是原子力显微镜(AFM),在这方面提供了坚实的贡献。此外,支撑平面双层膜(SPB)已成为研究脂质相互作用的一种成熟的膜模型。然而,尽管在这一领域发表了大量的结果,但数据仍然是分散的,并且缺少一个便于研究者访问的连贯的收集。本文总结了我们实验室在可比实验条件下使用AFM获得的相关结果,提供了支持脂质双分子层厚度和突破力的数据集合。广泛的脂质组成,包括磷脂,胆固醇和鞘脂(鞘磷脂,神经酰胺),在不同的分子比例,已被考虑。
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引用次数: 0
Stabilization of milk-sphingomyelin gel phases by glycosphingolipids: An in-vitro study on the characteristics of milk sphingolipid gel phases 鞘脂糖对乳鞘磷脂凝胶相的稳定作用:乳鞘脂凝胶相特性的体外研究。
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-15 DOI: 10.1016/j.chemphyslip.2025.105526
Md Abdullah Al Sazzad , Max Lönnfors , Baoru Yang
Sphingolipids constitute a class of bioactive lipids essential for the structural and functional integrity of milk fat globule membrane (MFGM). Milk sphingomyelin (milk-SM), as a key component of MFGM, contributes to the stability of milk fat emulsions. Milk-SM and other sphingolipids, like glycosphingolipids (GSL), coexist in the same outer bilayer of MFGM, suggesting significant role of their interaction in shaping the structural properties and functions of MFGM. In this study, using an in-vitro model membrane system, we investigated the impact of various GSLs, including cerebrosides and gangliosides, on the lateral segregation and phase behavior of milk-SM in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers. We also incorporated N-palmitoyl-D-erythro-ceramide for a comparative analysis of the impacts of sphingolipid head groups. The lateral segregation of sphingolipid gel phases was assessed using trans-parinaric acid (tPA) fluorescence lifetime analysis, and their thermostability was examined using steady-state fluorescence anisotropy of tPA. Additionally, we assessed the binary interactions between milk-SM and GSLs using the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH). The results indicate that GSLs promote the lateral segregation and stabilization of milk-SM-rich gel phases in the membrane bilayers. The size of the GSL head groups significantly influenced the degree of this stabilization, with larger head groups demonstrating diminished interactions with milk-SM. Our results provide valuable insights into the role of various sphingolipid structures in membrane phase behavior and organization. Comprehensive understanding of the interactions of these important sphingolipids in MFGM environment is crucial due to their structural and functional importance in dairy and nutritional applications.
鞘脂是一类生物活性脂类,对乳脂球膜的结构和功能完整性至关重要。乳鞘磷脂(Milk sphingomyelin, Milk - sm)作为MFGM的关键成分,对乳脂乳剂的稳定性起着重要作用。Milk-SM和鞘脂糖(GSL)等鞘脂共存于MFGM的同一外双分子层,表明它们的相互作用在MFGM的结构特性和功能形成中起着重要作用。在这项研究中,我们使用体外模型膜系统,研究了各种GSLs,包括脑苷和神经节苷,对乳sm在1-棕榈酰-2-油酰-sn-甘油-3-磷脂胆碱双层中的侧向分离和相行为的影响。我们还加入了n -棕榈酰- d -红-神经酰胺,对鞘脂头组的影响进行了比较分析。利用反式parinaric酸(tPA)荧光寿命分析评估鞘脂凝胶相的侧向分离,并利用tPA的稳态荧光各向异性检测其热稳定性。此外,我们利用1,6-二苯基-1,3,5-己三烯(DPH)的稳态荧光各向异性评估了牛奶- sm和GSLs之间的二元相互作用。结果表明,GSLs促进了膜双层中富乳- sm凝胶相的侧向分离和稳定。GSL头群的大小显著影响了这种稳定的程度,较大的头群显示出与牛奶sm的相互作用减弱。我们的结果为鞘脂结构在膜相行为和组织中的作用提供了有价值的见解。全面了解这些重要鞘脂在MFGM环境中的相互作用是至关重要的,因为它们在乳制品和营养应用中的结构和功能的重要性。
{"title":"Stabilization of milk-sphingomyelin gel phases by glycosphingolipids: An in-vitro study on the characteristics of milk sphingolipid gel phases","authors":"Md Abdullah Al Sazzad ,&nbsp;Max Lönnfors ,&nbsp;Baoru Yang","doi":"10.1016/j.chemphyslip.2025.105526","DOIUrl":"10.1016/j.chemphyslip.2025.105526","url":null,"abstract":"<div><div>Sphingolipids constitute a class of bioactive lipids essential for the structural and functional integrity of milk fat globule membrane (MFGM). Milk sphingomyelin (milk-SM), as a key component of MFGM, contributes to the stability of milk fat emulsions. Milk-SM and other sphingolipids, like glycosphingolipids (GSL), coexist in the same outer bilayer of MFGM, suggesting significant role of their interaction in shaping the structural properties and functions of MFGM. In this study, using an <em>in-vitro</em> model membrane system, we investigated the impact of various GSLs, including cerebrosides and gangliosides, on the lateral segregation and phase behavior of milk-SM in 1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphocholine bilayers. We also incorporated N-palmitoyl-D-erythro-ceramide for a comparative analysis of the impacts of sphingolipid head groups. The lateral segregation of sphingolipid gel phases was assessed using <em>trans</em>-parinaric acid (tPA) fluorescence lifetime analysis, and their thermostability was examined using steady-state fluorescence anisotropy of tPA. Additionally, we assessed the binary interactions between milk-SM and GSLs using the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH). The results indicate that GSLs promote the lateral segregation and stabilization of milk-SM-rich gel phases in the membrane bilayers. The size of the GSL head groups significantly influenced the degree of this stabilization, with larger head groups demonstrating diminished interactions with milk-SM. Our results provide valuable insights into the role of various sphingolipid structures in membrane phase behavior and organization. Comprehensive understanding of the interactions of these important sphingolipids in MFGM environment is crucial due to their structural and functional importance in dairy and nutritional applications.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"271 ","pages":"Article 105526"},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hydrogenous and deuterated phospholipid extracts from Escherichia coli as biomimetic cytoplasmic bacterial membranes 从大肠杆菌中提取的氢磷脂和氘磷脂作为仿生细胞质细菌膜。
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-14 DOI: 10.1016/j.chemphyslip.2025.105515
Giacomo Corucci , Pablo Sánchez-Puga , Krishna Chaithanya Batchu , Nicolò Paracini , Samantha Micciulla , Valérie Laux , Javier Carrascosa-Tejedor , Moritz Paul Karl Frewein , Yoshiki Yamaryo-Botté , Cyrille Botté , Giovanna Fragneto , Alessandra Luchini
Model lipid bilayers, reconstituted by using bacterial lipid extracts, are reliable systems to investigate the physical properties of bacterial membranes, and can be used, for example, to aid the design of new antibiotics. Here, we discuss the optimisation of a protocol for the production of hydrogenous and deuterated glycerophospholipid (GPL) extracts from Escherichia coli, and their reconstitution into model membranes. This protocol stands apart from state-of-the-art methods by introducing an additional purification step, which ensures a better separation of the GPL molecules from other membrane components such as neutral lipids. The composition of these extracts was characterised with different analytical methods. Experimental conditions were optimised for producing bacterial membrane models in the form of vesicles, lipid monolayers at the air/water interface and supported lipid bilayers. A combination of biophysical techniques, including Langmuir isotherms, neutron reflectometry, quartz crystal microbalance with dissipation monitoring, and small angle X-ray scattering provided detailed information on the self-assembled structures, and highlighted interesting differences between hydrogenous and deuterated extracts. Altogether, we report a detailed description of extraction and characterisation of hydrogenous and deuterated E. coli GPL extracts. The study of such complex lipid mixtures is important to recreate highly biologically relevant bacterial membrane models for studies aimed at understanding the biological function of bacterial membranes.
通过细菌脂质提取物重建的模型脂质双层是研究细菌膜物理性质的可靠系统,例如,可以用于帮助设计新的抗生素。在这里,我们讨论了从大肠杆菌中生产氢和氘化甘油磷脂(GPL)提取物的方案的优化,并将其重组为模型膜。该方案通过引入额外的纯化步骤,确保GPL分子与其他膜组分(如中性脂类)的更好分离,从而与最先进的方法不同。用不同的分析方法对这些提取物的成分进行了表征。优化实验条件,以制备囊泡、空气/水界面脂质单层和支撑脂质双层形式的细菌膜模型。生物物理技术的结合,包括Langmuir等温线、中子反射法、带耗散监测的石英晶体微平衡和小角度x射线散射,提供了自组装结构的详细信息,并突出了氢和氘萃取物之间的有趣差异。总之,我们报告了提取和表征氢和氘化大肠杆菌GPL提取物的详细描述。研究这种复杂的脂质混合物对于重建高度生物相关的细菌膜模型非常重要,旨在了解细菌膜的生物学功能。
{"title":"Hydrogenous and deuterated phospholipid extracts from Escherichia coli as biomimetic cytoplasmic bacterial membranes","authors":"Giacomo Corucci ,&nbsp;Pablo Sánchez-Puga ,&nbsp;Krishna Chaithanya Batchu ,&nbsp;Nicolò Paracini ,&nbsp;Samantha Micciulla ,&nbsp;Valérie Laux ,&nbsp;Javier Carrascosa-Tejedor ,&nbsp;Moritz Paul Karl Frewein ,&nbsp;Yoshiki Yamaryo-Botté ,&nbsp;Cyrille Botté ,&nbsp;Giovanna Fragneto ,&nbsp;Alessandra Luchini","doi":"10.1016/j.chemphyslip.2025.105515","DOIUrl":"10.1016/j.chemphyslip.2025.105515","url":null,"abstract":"<div><div>Model lipid bilayers, reconstituted by using bacterial lipid extracts, are reliable systems to investigate the physical properties of bacterial membranes, and can be used, for example, to aid the design of new antibiotics. Here, we discuss the optimisation of a protocol for the production of hydrogenous and deuterated glycerophospholipid (GPL) extracts from <em>Escherichia coli</em>, and their reconstitution into model membranes. This protocol stands apart from state-of-the-art methods by introducing an additional purification step, which ensures a better separation of the GPL molecules from other membrane components such as neutral lipids. The composition of these extracts was characterised with different analytical methods. Experimental conditions were optimised for producing bacterial membrane models in the form of vesicles, lipid monolayers at the air/water interface and supported lipid bilayers. A combination of biophysical techniques, including Langmuir isotherms, neutron reflectometry, quartz crystal microbalance with dissipation monitoring, and small angle X-ray scattering provided detailed information on the self-assembled structures, and highlighted interesting differences between hydrogenous and deuterated extracts. Altogether, we report a detailed description of extraction and characterisation of hydrogenous and deuterated <em>E. coli</em> GPL extracts. The study of such complex lipid mixtures is important to recreate highly biologically relevant bacterial membrane models for studies aimed at understanding the biological function of bacterial membranes.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"271 ","pages":"Article 105515"},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of gramicidin A on the constant tension-induced rupture of giant unilamellar vesicles and the underlying mechanisms gramicidin A对恒定张力诱导的巨大单层囊泡破裂的影响及其机制
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-07 DOI: 10.1016/j.chemphyslip.2025.105525
Mir Jubair Ahamed , Tawfika Nasrin , Zarin Tasnim Rakhy , Md. Masum Billah , Mohammad Abu Sayem Karal
Gramicidin A (GrA), a well-known ionophore, plays a significant role in modifying the biophysical properties of membranes. However, its mechanism of action in influencing rupture kinetics of vesicles and the stability of membranes under constant mechanical tension remains unclear. To investigate this, giant unilamellar vesicles (GUVs) composed of DOPG and DOPC phospholipids, with varying molar fractions of GrA (ranging from 0 % to 5 %), were synthesized using the natural swelling method. These GUVs were then subjected to mechanical tension using the micropipette aspiration technique. The rupture kinetics were assessed by quantifying the fraction of intact vesicles over time under a fixed mechanical tension, allowing the determination of the rupture rate constant. The results revealed a non-monotonic effect of GrA on membrane rupture: at low concentrations (up to 1 % GrA), GUVs exhibited increased structural stability, while at higher concentrations (1–5 % GrA), rupture probability significantly increased. Additionally, the area compressibility modulus of the GUV membranes was evaluated, showing that GrA incorporation led to alterations in membrane elasticity. These findings provide insights into the molecular mechanisms by which GrA modulates membrane integrity under mechanical stress, offering valuable implications for biophysical studies of ionophore-lipid interactions and membrane stability in biological systems.
Gramicidin A (GrA)是一种众所周知的离子载体,在改变膜的生物物理性质方面起着重要作用。然而,其在恒定机械张力下影响囊泡破裂动力学和膜稳定性的作用机制尚不清楚。为了研究这一点,采用自然膨胀法合成了由DOPG和DOPC磷脂组成的巨大单层囊泡(GUVs),其GrA的摩尔分数为0 %至5 %。然后使用微管抽吸技术对这些guv施加机械张力。在固定的机械张力下,通过定量完整囊泡随时间的比例来评估破裂动力学,从而确定破裂率常数。结果显示,GrA对膜破裂具有非单调效应:在低浓度(高达1 % GrA)下,guv表现出更高的结构稳定性,而在高浓度(1 - 5 % GrA)下,破裂概率显著增加。此外,对GUV膜的面积压缩模量进行了评估,表明GrA的掺入导致了膜弹性的改变。这些发现提供了GrA在机械应力下调节膜完整性的分子机制的见解,为生物系统中离子载体-脂质相互作用和膜稳定性的生物物理研究提供了有价值的意义。
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引用次数: 0
Role of water in the responsiveness of lipid membranes: Application of non-equilibrium thermodynamics 水在脂质膜反应性中的作用:非平衡热力学的应用
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-06-17 DOI: 10.1016/j.chemphyslip.2025.105514
E. Anibal Disalvo, Jimena del P. Cejas, Agustín González Paz, María de los A. Frías
The phenomenological description of a lipid membrane within the frame of the interphase model in which membrane is a bidimensional solution of hydrated lipids allows to make compatible the membrane theory and Ling hypothesis by considering the physical chemical properties of the aqueous lipid interphase.
The membrane suffers mechanical stress inducing changes in hydration and changes in composition. These conditions affect the amount of labile active water propense to response to bioeffectors. This behavior is properly described with the approach of thermodynamic of irreversible processes in which the membrane is an open system and is in a metastable state propense to react due to bioeffectors in the adjacent aqueous solution. In terms of this analysis, the hydration shell is inert to bioeffectors and the response of the membrane is given by the excess of water that is labile and osmotically exchangeable.
在间期模型框架内对脂质膜的现象学描述,其中膜是水合脂质的二维溶液,通过考虑水质间期的物理化学性质,可以使膜理论和Ling假说相容。膜受到机械应力,导致水合作用和成分的变化。这些条件影响不稳定活性水的数量倾向于对生物效应剂的反应。这种行为可以用不可逆过程的热力学方法恰当地描述,在不可逆过程中,膜是一个开放系统,由于邻近水溶液中的生物效应物而处于亚稳态,倾向于发生反应。根据这一分析,水合壳对生物效应物是惰性的,膜的反应是由多余的不稳定和渗透交换的水给予的。
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引用次数: 0
Location and dynamics of astaxanthin in the membrane 虾青素在膜中的位置和动态。
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-06-14 DOI: 10.1016/j.chemphyslip.2025.105512
José Villalaín
Astaxanthin (ASX) is a natural xanthophyll carotenoid recognized for its strong antioxidant bioactive function, and it has been used in the prevention of heart disease, inflammation, neurological disorders, scavenger of environmental produced free radicals and as an anti-aging and anti-cancer biomolecule. ASX is a long lipophilic molecule with two terminal relatively polar rings connected by a long hydrophobic chain. This work describes the dynamics, orientation, location and interactions of ASX in a complex biomembrane. In water, ASX form high-order aggregates where the molecules are joined together by the hydrophobic chain. Depending on the number of ASX molecules, the aggregates can have different structures and the polar groups positioned superficially contacting the solvent. ASX molecules are not able to insert themselves into the membrane, forming high-order aggregates quickly. In the membrane, ASX molecules do not aggregate, remaining all time in the monomeric state. ASX is capable of reaching both membrane surfaces, one at a time. The ASX molecules form an approximate angle of 20º with respect to the membrane perpendicular and it is inserted between the phospholipid hydrocarbon chains, increasing slightly the membrane fluidity. ASX is readily miscible with membrane phospholipids and its location within the membrane is suited for its potent antioxidant activity. Furthermore, since ASX has two polar groups at both ends, the molecule can function in a wide range of depths. ASX is therefore perfectly suited for its antioxidant task in the membrane.
虾青素(Astaxanthin, ASX)是一种天然的类胡萝卜素类叶黄素,具有较强的抗氧化活性,被广泛应用于预防心脏病、炎症、神经系统疾病、清除环境产生的自由基以及抗衰老、抗癌等生物分子。ASX是一种长亲脂分子,具有两个末端相对极性的环,由一条长疏水链连接。这项工作描述了动态,取向,位置和相互作用的ASX在一个复杂的生物膜。在水中,ASX形成高阶聚集体,其中分子通过疏水链连接在一起。根据ASX分子的数量,聚集体可以有不同的结构和极性基团定位在与溶剂接触的表面。ASX分子不能将自己插入到膜中,迅速形成高阶聚集体。在膜中,ASX分子不聚集,一直保持单体状态。ASX能够到达膜的两个表面,一次一个。ASX分子与膜垂直形成约20º的夹角,并插入磷脂烃链之间,略微增加膜的流动性。ASX很容易与膜磷脂混溶,其在膜内的位置适合其强大的抗氧化活性。此外,由于ASX在两端有两个极性基团,该分子可以在很宽的深度范围内发挥作用。因此,ASX非常适合其在膜中的抗氧化任务。
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引用次数: 0
Interaction between lactic acid bacteria and bile acids: Molecular and biophysical insights 乳酸菌和胆汁酸之间的相互作用:分子和生物物理的见解。
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-06-14 DOI: 10.1016/j.chemphyslip.2025.105513
A.Y. Bustos , M.P. Taranto
Dynamic interactions between microbes and host are essential to stimulate the immune system, maintain intestinal homeostasis, and prevent pathogen colonization. In recent decades lactic acid bacteria (LAB) have received attention due to their probiotic potential and their impact on gut microbiota and host health. This paper aims to review the main molecular mechanisms by which bile acids (BA) modify the composition of the intestinal microbiota and bacterial viability, with special emphasis on the effect on LAB. The results discussed here suggest that the BA disorganize the structure of the bacterial cell wall, modify their surface properties, their adhesion capacity and compromise the integrity of the membranes, with loss of essential ions and nutrients. They then enter the cell interior, at rates that depend on their hydrobicity. There, they dissociate, causing intracellular acidification and dissipation of membrane potential. This leads to a deficiency in the biological energy needed for critical processes, leading to cell death at high concentrations. In addition, BA causes alteration and oxidation of proteins and nucleic acids. The extent of damage caused by BA is influenced by their structure, physicochemical properties—particularly hydrophobicity—and concentration. The response of LAB depends on both their intrinsic and adaptive mechanisms. Advancing research on these interactions represents a new frontier, enabling the development of strategies to modulate intestinal microbiota composition, ultimately benefiting human health.
微生物与宿主之间的动态相互作用对刺激免疫系统、维持肠道稳态和防止病原体定植至关重要。近几十年来,乳酸菌因其益生菌潜力及其对肠道菌群和宿主健康的影响而受到人们的关注。本文旨在综述胆汁酸(BA)改变肠道菌群组成和细菌活力的主要分子机制,重点介绍其对乳酸菌的影响。本文讨论的结果表明,BA破坏了细菌细胞壁的结构,改变了它们的表面性质和粘附能力,损害了细胞膜的完整性,损失了必需离子和营养物质。然后它们进入细胞内部,其速率取决于它们的水合性。在那里,它们解离,引起细胞内酸化和膜电位的耗散。这导致关键过程所需的生物能缺乏,导致高浓度的细胞死亡。此外,BA引起蛋白质和核酸的改变和氧化。胆汁酸(BA)造成的损害程度受其结构、理化性质(特别是疏水性)和浓度的影响。乳酸菌(LAB)的应答取决于其内在的和适应性的耐药机制。推进对这些相互作用的研究代表了一个新的前沿,使调节肠道微生物群组成的策略得以发展,最终有益于人类健康。
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Chemistry and Physics of Lipids
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