Biochimica et biophysica acta. Biomembranes最新文献_第3页

Study of the effects of phenolic acids and their triphenylphosphonium derivatives on the permeability and state of liposomal membrane, the functional activity of isolated rat liver mitochondria, and the survival of MCF-7 cells 酚酸及其三苯磷衍生物对脂质体膜通透性、状态、离体大鼠肝线粒体功能活性及MCF-7细胞存活的影响

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-12 DOI: 10.1016/j.bbamem.2025.184473

Mikhail V. Dubinin , Anna I. Ilzorkina , Anastasia D. Igoshkina , Natalia V. Mikina , Rezeda R. Khalitova , Nikita V. Penkov , Natalia V. Belosludtseva , Anna Y. Spivak , Konstantin N. Belosludtsev

This study shows the effects of phenolic acids (gallic, coumaric, caffeic, and ferulic) and their triphenylphosphonium (TPP⁺) derivatives on the state of liposomal membrane, the functioning of isolated rat liver mitochondria, and the survival of MCF-7 breast adenocarcinoma cells. It was demonstrated that alkyltriphenylphosphonium esters of phenolic acids in contrast to their parental compounds, increase liposome membrane permeability to sulforhodamine B without altering their phase state. These derivatives also exhibit uncoupling effects on oxidative phosphorylation, reducing membrane potential and stimulating oxygen consumption in mitochondria fueled by glutamate/malate (substrate for complex I of the respiratory chain) or succinate (substrate for complex II). In addition, the compounds reduced the ability of mitochondria to uptake and retain Ca²⁺, suggesting their influence on calcium homeostasis. Conjugation of phenolic acids with the TPP⁺ moiety significantly enhanced their cytotoxic effects on MCF-7 cells. This study establishes a clear structure-activity relationship, demonstrating that conjugation with TPP⁺ via an ester linker is an advantageous strategy for enhancing the mitochondrial targeting and bioactivity of phenolic acids compared to amide linkage or the parental compounds.

本研究揭示了酚酸（没食子酸、香豆酸、咖啡酸和阿魏酸）及其三苯基膦（TPP+）衍生物对脂质体膜状态、离体大鼠肝脏线粒体功能和MCF-7乳腺腺癌细胞存活的影响。结果表明，与亲本化合物相比，酚酸的烷基三苯磷酯增加了脂质体膜对磺胺丹B的渗透性，而不改变其相态。这些衍生物还表现出氧化磷酸化解偶联作用，降低膜电位，刺激线粒体中由谷氨酸/苹果酸盐（呼吸链复合体I的底物）或琥珀酸盐（复合体II的底物）提供燃料的氧消耗。此外，这些化合物降低了线粒体摄取和保留Ca2+的能力，表明它们对钙稳态的影响。酚酸与TPP+片段的偶联显著增强了它们对MCF-7细胞的细胞毒性作用。本研究建立了清晰的构效关系，表明与酰胺连接或亲本化合物相比，通过酯连接物与TPP+结合是增强酚酸线粒体靶向性和生物活性的有利策略。

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引用次数: 0

Immune antibodies recognizing the stem region of SARS-CoV-2 spike protein: Molecular modeling and in vitro study of synthetic peptides presentation to the antibodies 识别SARS-CoV-2刺突蛋白茎区的免疫抗体：分子模型和合成肽向抗体呈递的体外研究

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-12 DOI: 10.1016/j.bbamem.2025.184472

Elena T. Aliper , Ivan M. Ryzhov , Polina S. Obukhova , Alexander B. Tuzikov , Oxana E. Galanina , Marina M. Ziganshina , Gennady T. Sukhikh , Nikolay A. Krylov , Stephen M. Henry , Roman G. Efremov , Nicolai V. Bovin

Antibodies to peptide 1147 (amino acids 1147–61) of the SARS-CoV-2 S protein are highly diagnostic. Peptide 1147, although located in a region that is partly spatially hidden in the intact protein, is not subject to mutations, suggesting therapeutic potential. The aim of this study was to elucidate the architecture of this region and the way in which it is presented to antibodies. As a model system, this peptide carrying a single lipophilic tail and the same peptide carrying a lipophilic tail at both ends (pseudocyclic) were incorporated into a lipid membrane. Isolated anti-1147 antibodies interacted with it regardless of how the peptide was presented, be that freely exposed via the N-terminus, organized as a pseudocycle, or adsorbed on the surface. Molecular dynamics simulations showed that peptide 1147 is capable of closely approaching the membrane. Analysis of the surface properties of peptide 1147 in membrane-bound states and in particular functional conformations in the full-sized S protein reveals an interface for interaction with antibodies. Interestingly, the latter bears similarities to one published peptide-antibody complex. However, these antibodies, in spite of their high diagnostic significance, show no virus-neutralizing activity, indicating that peptide 1147 has no therapeutic value as a synthetic vaccine.

针对sars - cov - 2s蛋白肽1147（氨基酸1147-61）的抗体具有很高的诊断价值。肽1147虽然位于部分空间隐藏在完整蛋白中的区域，但不受突变的影响，提示治疗潜力。这项研究的目的是阐明该区域的结构和它是如何呈现给抗体的。作为一个模型系统，这种携带单亲脂尾的肽和两端携带亲脂尾的同一肽（伪环）被纳入脂质膜。无论肽如何呈现，分离的抗1147抗体都与它相互作用，无论是通过n端自由暴露，组织为假环，还是吸附在表面。分子动力学模拟表明，肽1147能够接近细胞膜。分析肽1147在膜结合状态下的表面特性，特别是在全尺寸S蛋白中的功能构象，揭示了与抗体相互作用的界面。有趣的是，后者与一种已发表的肽抗体复合物有相似之处。然而，尽管这些抗体具有很高的诊断意义，但却没有病毒中和活性，这表明肽1147作为合成疫苗没有治疗价值。

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引用次数: 0

The relationship between the structural transitions of DMPG membranes and the melting process, and their interaction with water DMPG膜的结构转变与熔融过程的关系及其与水的相互作用。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-10 DOI: 10.1016/j.bbamem.2025.184475

Thomas Heimburg , Holger Ebel , Peter Grabitz , Julia Preu , Yue Wang

During the melting transition of dimyristoyl phosphatidylglycerol (DMPG), the order of the lipid chains and the three-dimensional, vesicular structural arrangement change simultaneously. These changes result in peculiar heat capacity profiles extended over a broad temperature range with several

c_{p}

-maxima. Here, we present calorimetric, viscosity, and volume expansion coefficient data at various ionic strengths and charges. We propose a simple theory that explains the calorimetric data in terms of the coexistence of two membrane geometries, both of which can melt. During the transition, the equilibrium between these two geometries changes cooperatively. This equilibrium depends on the interactions between the membranes and the solvent, on the membrane’s charge and the ionic strength of the buffer. Solvent interactions also contribute to the volume change of the membrane phases. Unlike uncharged membranes, we find that enthalpy changes are no longer proportional to volume changes. Therefore, the pressure dependence of the calorimetric profiles differs from that of uncharged membranes. Our theory explains the pressure dependence of calorimetric profiles qualitatively and quantitatively. Furthermore, we demonstrate that the same theory can be used to describe pretransition and ripple formation in phosphatidylcholines. A key takeaway from this article is that solvent molecules (e.g., H

_{2}

O) are part of the membrane and, in the case of DMPG, water cannot be considered a separate phase.

二myristoyl磷脂酰甘油（DMPG）在熔融转变过程中，脂链的顺序和三维囊泡结构排列同时发生变化。这些变化导致特殊的热容分布，扩展到具有7个cp最大值的宽温度范围。在这里，我们给出了不同离子强度和电荷下的量热、粘度和体积膨胀系数数据。我们提出了一个简单的理论来解释两种膜几何形状共存的量热数据，这两种膜都可以熔化。在过渡过程中，这两种几何形状之间的平衡协同变化。这种平衡取决于膜和溶剂之间的相互作用，取决于膜的电荷和缓冲液的离子强度。溶剂的相互作用也有助于膜相的体积变化。不像不带电的膜，我们发现焓的变化不再与体积的变化成正比。因此，热谱图的压力依赖性不同于不带电膜。我们的理论定性和定量地解释了量热剖面的压力依赖性。此外，我们证明了相同的理论可以用来描述磷脂酰胆碱的预转变和波纹形成。本文的一个关键结论是，溶剂分子（例如H2O）是膜的一部分，在DMPG的情况下，水不能被认为是一个单独的相。

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引用次数: 0

MPP1 controls lipid domain remodelling in giant vesicles containing reconstituted flotillins MPP1控制含有重组浮细胞的巨囊泡中的脂质结构域重塑。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-06 DOI: 10.1016/j.bbamem.2025.184471

Agnieszka Chytła , Agnieszka Biernatowska , Weronika Gajdzik-Nowak , Aleksander F. Sikorski , Aleksander Czogalla

Membrane palmitoylated protein 1 (MPP1), a protein found to directly interact with flotillins, has been shown to play a crucial role as a raft-capturing molecule, modulating dynamics of flotillin-nanodomains and affects plasma membrane (PM) organisation in native erythroid cells. This study aims to reconstitute the flotillin-MPP1 complexes in a minimal membrane-based system to check its ability to govern domain formation and modulate fluidity and phase separation of membranes comprising simple ternary lipid mixtures. Using recombinant flotillins reconstituted into giant unilamellar vesicles (GUVs) and fluorescence lifetime imaging (FLIM), we have shown that MPP1 promotes membrane remodelling and triggers the coexistence of liquid-ordered (L_o) and liquid-disordered (L_d) domains. Additionally, we examined whether palmitoylation of MPP1 affects lipid bilayers and demonstrated that it exerts a certain influence on membrane organisation. Our data highlights that flotillin-MPP1 assemblies are sufficient and necessary to modulate the lateral organisation of lipid bilayers, pointing to their crucial role in PM organisation. Additionally, we propose a new toolset for successful flotillin reconstitution in GUVs, which is a viable platform compatible with a wide spectrum of flotillin-based studies on model membrane systems.

膜棕榈酰化蛋白1 （MPP1）是一种被发现与flotillins直接相互作用的蛋白，已被证明作为一种筏子捕获分子起着至关重要的作用，调节flotillins纳米结构域的动力学并影响原生红细胞的质膜（PM）组织。本研究旨在在最小的膜基系统中重建flotillin-MPP1复合物，以检查其控制结构域形成和调节由简单三元脂质混合物组成的膜的流动性和相分离的能力。通过重组成巨型单层囊泡（GUVs）和荧光寿命成像（FLIM），我们发现MPP1促进膜重塑并触发液体有序（Lo）和液体无序（Ld）结构域的共存。此外，我们研究了MPP1棕榈酰化是否影响脂质双分子层，并证明它对膜组织有一定的影响。我们的数据强调flotillin-MPP1组装体是调节脂质双分子层横向组织的充分和必要的，指出它们在PM组织中的关键作用。此外，我们还提出了一套新的工具集，用于guv中成功的浮力重构，该工具集是一个可行的平台，可用于基于浮力的模型膜系统研究。

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引用次数: 0

Lateral lipid packing governs bilayer solubilization by styrene-maleic acid copolymers: a case study with cardiolipin-containing membranes 侧脂质填料支配着苯乙烯-马来酸共聚物的双层增溶：含心磷脂膜的案例研究。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-05 DOI: 10.1016/j.bbamem.2025.184470

Joseph C. Iovine , Benjamin T. Garrett , Nathan N. Alder

Styrene-maleic acid (SMA) copolymers are powerful tools for the detergent-free solubilization of biological membranes. Yet the influence of specific lipids on SMA activity remains an open question. Here, we examined the effects of the mitochondria-specific phospholipid cardiolipin on SMA-mediated membrane solubilization and its ability to form SMA-bound nanodiscs. To this end, we prepared a series of model membranes with cardiolipin and other test lipids with comparable surface charge and lateral packing characteristics. Using multiple independent experimental approaches, we found that cardiolipin inhibited SMA solubilization. Our results indicate that this effect was not attributable to headgroup charge effects, but related to cardiolipin-induced increase in lateral packing pressure at the interfacial region. Reduction of this lateral packing pressure using bilayer-active alcohols partially restored SMA solubilization. Our results highlight the importance of lipid geometry and packing in SMA nanodisc formation and could help guide the design of copolymers tailored to specific membranes.

苯乙烯-马来酸（SMA）共聚物是生物膜无洗涤剂增溶的有力工具。然而，特定脂类对SMA活性的影响仍然是一个悬而未决的问题。在这里，我们研究了线粒体特异性磷脂心磷脂对sma介导的膜增溶及其形成sma结合纳米盘的能力的影响。为此，我们制备了一系列模型膜，其中含有心磷脂和其他具有类似表面电荷和横向包装特性的测试脂质。通过多个独立的实验方法，我们发现心磷脂抑制SMA的增溶。我们的研究结果表明，这种影响不是归因于头群电荷效应，而是与心磷脂诱导的界面区域侧堆积压力的增加有关。使用双层活性醇降低侧封压力，部分恢复了SMA的增溶作用。我们的研究结果强调了脂质几何形状和填充在SMA纳米盘形成中的重要性，并有助于指导针对特定膜定制共聚物的设计。

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引用次数: 0

Transmembrane channel-like 4 (TMC4) could act as a negative regulator of KCNQ1 (Kv7.1) potassium channel 跨膜通道样4 （TMC4）可作为KCNQ1 （Kv7.1）钾通道的负调控因子。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-02 DOI: 10.1016/j.bbamem.2025.184460

Hirota Aoyagi, Koya Kawaguchi, Saori Yano-Nashimoto, Soichiro Yamaguchi

TMC4 is a member of the transmembrane channel-like (TMC) protein family. In this family, TMC1 and TMC2 are thought to form the mechano-electrical transduction (MET) channel in the inner ear. On the other hand, the intrinsic functions of the other TMC family members (TMC3-8) are largely unknown. KCNQ1 (Kv7.1) channel is a voltage-gated potassium channel and plays crucial physiological roles with its auxiliary subunits, KCNE proteins (e.g. KCNQ1/KCNE1 complex contributes to cardiac repolarization, and KCNQ1/KCNE3 complex participates in epithelial ion transport). Recently, it was reported that TMC1 and TMC2 interacted with KCNQ1 and suppressed its K⁺ currents. However, the relationships between KCNQ1 and the other TMC proteins have not been examined. Here, we show a novel interaction and a functional association between overexpressed TMC4 and KCNQ1. The Bead Halo assay and FRET analysis revealed the physical interaction between these two proteins. Whole-cell patch clamp recording demonstrated that co-expression of TMC4 reduced KCNQ1 current densities without altering their voltage dependence and activation kinetics. This effect was also observed in the KCNQ1/KCNE1 and KCNQ1/KCNE3 channel complexes. A structural prediction using AlphaFold-Multimer suggested possible interaction sites between TMC4 and KCNQ1. Mutageneses, followed by patch clamp recording, suggested that specific amino acid residues at these sites contribute to the inhibitory effect of TMC4. These results indicate that TMC4 could function as a negative regulator of the KCNQ1 channel. Our findings could enhance the understanding of KCNQ1 channel regulation and propose potential research directions on the function of TMC4 under various physiological and pathological conditions.

TMC4是跨膜通道样（TMC）蛋白家族的成员。在这个家族中，TMC1和TMC2被认为在内耳形成机电转导（MET）通道。另一方面，其他TMC家族成员（TMC3-8）的内在功能很大程度上是未知的。KCNQ1 （Kv7.1）通道是电压门控钾通道，其辅助亚基KCNE蛋白（如KCNQ1/KCNE1复合体参与心脏复极化，KCNQ1/KCNE3复合体参与上皮离子运输）在生理上发挥重要作用。最近有报道称，TMC1和TMC2与KCNQ1相互作用，抑制KCNQ1的K+电流。然而，KCNQ1与其他TMC蛋白之间的关系尚未被研究。在这里，我们展示了过表达的TMC4和KCNQ1之间的一种新的相互作用和功能关联。head Halo试验和FRET分析揭示了这两种蛋白之间的物理相互作用。全细胞膜片钳记录显示，TMC4的共表达降低了KCNQ1电流密度，但没有改变它们的电压依赖性和激活动力学。在KCNQ1/KCNE1和KCNQ1/KCNE3通道复合物中也观察到这种效应。利用AlphaFold-Multimer进行结构预测，发现TMC4和KCNQ1之间可能存在相互作用位点。诱变后膜片钳记录表明，这些位点上的特定氨基酸残基有助于TMC4的抑制作用。这些结果表明，TMC4可以作为KCNQ1通道的负调节因子。我们的发现可以加深对KCNQ1通道调控的认识，并为TMC4在各种生理和病理条件下的功能提供潜在的研究方向。

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引用次数: 0

Unveiling the impact of membrane fluidity in shaping lipid-based drug delivery systems development 揭示膜流动性在塑造脂基药物输送系统发展中的影响。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-02 DOI: 10.1016/j.bbamem.2025.184461

Mariana Biscaia-Caleiras , Ana Sofia Lourenço , João Nuno Moreira , Sérgio Simões

Membrane fluidity is a fundamental property extensively studied in biological membranes and biophysical research, where it is critical to understanding membrane structure and function. However, its application in the development and manufacturing of lipid-based drug delivery systems, such as liposomes and lipid nanoparticles, remains underexplored. This mini-review shifts the focus toward the practical implications of membrane fluidity in pharmaceutical formulation and manufacturing. We highlight key factors influencing fluidity, such as temperature, lipid composition, and cholesterol content, and emphasize how understanding and controlling fluidity can serve as a critical quality attribute. The importance of these factors in modulating membrane dynamics is emphasized, revealing their potential to optimize liposomal formulations and manufacturing processes. Fluorescent probes such as DPH and Laurdan are also discussed for their ability to monitor fluidity in real-time, each presenting distinct advantages and limitations. Although its crucial role in lipid-based drug delivery systems, membrane fluidity remains a largely overlooked property. Deeper investigation is essential to fully understand its influence on membrane stability, therapeutic efficacy, and scalability. This mini-review advocates for a paradigm shift: recognizing membrane fluidity as a critical quality attribute that can be integrated into formulation development and industrial manufacturing frameworks to better predict and control product performance and process robustness.

膜流动性是生物膜和生物物理研究中广泛研究的一个基本特性，对理解膜的结构和功能至关重要。然而，它在基于脂质体的药物输送系统（如脂质体和脂质纳米颗粒）的开发和制造中的应用仍未得到充分探索。这篇迷你评论将焦点转向了药物配方和制造中膜流动性的实际意义。我们强调了影响流动性的关键因素，如温度、脂质组成和胆固醇含量，并强调了如何理解和控制流动性可以作为关键的质量属性。强调了这些因素在调节膜动力学中的重要性，揭示了它们优化脂质体配方和制造过程的潜力。荧光探针如DPH和Laurdan也讨论了他们实时监测流动性的能力，每个都有不同的优势和局限性。尽管它在脂质药物传递系统中起着至关重要的作用，但膜流动性仍然是一个很大程度上被忽视的特性。为了充分了解其对膜稳定性、治疗效果和可扩展性的影响，有必要进行更深入的研究。这篇小型综述提倡一种范式转变：认识到膜流动性是一个关键的质量属性，可以整合到配方开发和工业制造框架中，以更好地预测和控制产品性能和工艺稳健性。

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引用次数: 0

Temperature, pressure and salt effects on bilayers of an acidic phospholipid, dipalmitoylphosphatidylglycerol 温度、压力和盐对酸性磷脂双棕榈酰磷脂酰甘油双层结构的影响。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-02 DOI: 10.1016/j.bbamem.2025.184462

Masaki Goto , Saeko Tanaka , Nobutake Tamai , Hitoshi Matsuki

The effects of thermal pretreatments and a monovalent added salt (NaCl) on the thermotropic and barotropic bilayer phase behavior of an acidic phospholipid, dipalmitoylphosphatidylglycerol (DPPG), were investigated by differential scanning calorimetry, fluorometry and light transmittance measurements. At 1.0 mol kg⁻¹ NaCl concentration, lipid samples with static annealing treatments (i.e., cold storage) showed a transition from a metastable hydrated crystalline phase to the lamellar gel phase in addition to the pre- and the main transition. These transition temperatures increased with pressure and the interdigitated gel phase was induced under high pressure, which is similar to the bilayer phase behavior of dipalmitoylphosphatidylcholine. By contrast, lipid samples with dynamic annealing treatments (i.e., repeated freeze-thaw cycles) exhibited only a transition from the stable hydrated crystalline phase to the liquid crystalline phase accompanied by the morphological change in the bilayer aggregate. The transition temperature also increased with pressure and the phase behavior resembled that of dipalmitoylphosphatidylethanolamine. Regarding the salt effect, we found that the temperature–pressure phase diagrams of the non-annealed DPPG bilayer changed systematically with the salt concentration, demonstrating that the pressure-induced interdigitation is suppressed by the added salt. Thermodynamic quantities of the phase transitions increased with increasing salt concentration, suggesting that the DPPG bilayer was stabilized by the weakening of the electrostatic repulsion among the polar head groups due to the shielding effect. The concentration dependence of the minimum interdigitation pressure indicates the possibility that the interdigitation should occur even under atmospheric pressure in the absence of the salt.

采用差示扫描量热法、荧光法和透射率法研究了热预处理和一价添加盐（NaCl）对酸性磷脂双棕榈酰磷脂酰甘油（DPPG）热致和正压性双层相行为的影响。在1.0 mol kg-1 NaCl浓度下，经过静态退火（即冷藏）处理的脂质样品除了有预转变和主转变外，还出现了从亚稳水合结晶相到层状凝胶相的转变。这些转变温度随着压力的增加而升高，在高压下诱导出交叉的凝胶相，这与双棕榈酰磷脂酰胆碱的双层相行为相似。相比之下，经过动态退火处理（即反复冻融循环）的脂质样品只表现出从稳定的水合结晶相到液晶相的转变，并伴有双层聚集体的形态变化。转变温度随压力升高而升高，相行为与双棕榈酰磷脂酰乙醇胺相似。对于盐的影响，我们发现未退火的DPPG双分子层的温度-压力相图随着盐浓度的变化而发生系统的变化，表明盐的加入抑制了压力诱导的交叉作用。相变的热力学量随着盐浓度的增加而增加，表明由于屏蔽作用，极性头基之间的静电斥力减弱，使DPPG双分子层稳定。最小指间化压力的浓度依赖性表明，即使在没有盐的大气压力下，指间化也可能发生。

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引用次数: 0

Two phase coexistence in ternary mixtures of saturated and polyunsaturated phosphatidylcholines with cholesterol. 饱和和多不饱和磷脂酰胆碱与胆固醇三元混合物的两相共存。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1016/j.bbamem.2025.184436

James H Davis

Combining ²H and ¹⁴N nuclear magnetic resonance measurements on ternary lipid/cholesterol mixtures it is possible to quantitate the phase separation into coexisting ℓ_o and ℓ_d domains using a single sample whose composition is within the two phase region. Mixtures of each of the unsaturated phospholipids dioleoyl phosphatidylcholine, dilinoleoyl phosphatidylcholine and dilinolenoyl phosphatidylcholine with the saturated dipalmitoyl phosphatidylcholine and cholesterol all exhibit ℓ_o and ℓ_d phase coexistence over a substantial range of compositions and temperatures. A higher degree of unsaturation broadens the temperature range of two phase coexistence and results in the ℓ_d phase domains actually being significantly more 'fluid' at lower temperatures than they are at higher temperatures.

结合对三元脂/胆固醇混合物的2H和14N核磁共振测量，可以使用一个组成在两相区域内的单一样品来量化相分离到共存的_o和_d域。每一种不饱和磷脂二酰磷脂酰胆碱、二酰磷脂酰胆碱和二酰磷脂酰胆碱与饱和二棕榈酰磷脂酰胆碱和胆固醇的混合物在相当大的组成和温度范围内均表现出0和d相共存。较高的不饱和程度扩大了两相共存的温度范围，并导致在较低温度下的d相域实际上比在较高温度下更具有“流动性”。

引用次数: 0

Development of amyloid-cationic peptides with antimicrobial activities: Relation to their membranotropic activities. 具有抗菌活性的淀粉样阳离子肽的开发：与其膜性活性的关系。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1016/j.bbamem.2025.184439

Marta Balestra, Lilia Leghmizi, Thierry Drujon, Loïc Portier, Cillian Byrne, Fabienne Burlina, Sylvie Noinville

We describe here a new class of antimicrobial peptides (named Amy-Cat) comprised of a short amyloid domain and a cationic domain, as a primary amphipathic structure. The nona-arginine sequence was chosen as the cationic motif, while the sequence and size of the amyloid domain was modulated. The Amy-Cat peptides were found to be bactericidal against gram-negative and gram-positive standard bacterial strains with minimum inhibitory concentrations ranging from 3 to 24 μM, and being well-below their hemolytic concentrations. Their membranotropic activities were investigated as a function of the amyloid sequence and compared to those of the nona-arginine peptide. Calcein dye leakage on lipid mimic models for bacterial and eukaryotic membranes was carried out. In addition, the effect of the amyloid moiety on the membrane binding and on the conformational change were investigated at the buffer/supported lipid bilayer interface using ATR-FTIR spectroscopy. The overall findings suggest optimum routes to balancing the hydrophobicity of the amyloid sequence over the fixed cationic sequence allowing selective disruption of the bacterial membranes without eliciting hemolysis. Amy-Cat peptides appear to be very promising candidates for the development of new antimicrobial agents.

我们在这里描述了一类新的抗菌肽（命名为Amy-Cat），它由一个短淀粉样结构域和一个阳离子结构域组成，是一个主要的两亲结构。选择非精氨酸序列作为阳离子基序，同时调节淀粉样结构域的序列和大小。研究发现，ami - cat肽对革兰氏阴性和革兰氏阳性标准菌株具有杀菌作用，其最低抑菌浓度为3 ~ 24 μM，远低于其溶血浓度。它们的膜性活性作为淀粉样蛋白序列的功能进行了研究，并与nona-精氨酸肽进行了比较。研究了钙黄蛋白在细菌和真核生物膜脂质模拟模型上的渗漏。此外，利用ATR-FTIR光谱研究了淀粉样蛋白片段对缓冲/支撑脂质双层界面上膜结合和构象变化的影响。总的研究结果表明，平衡淀粉样蛋白序列在固定阳离子序列上的疏水性的最佳途径，允许在不引起溶血的情况下选择性地破坏细菌膜。Amy-Cat肽似乎是开发新型抗菌药物的非常有前途的候选者。

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引用次数: 0