钯纳米团簇诱导脂质过氧化和膜物理特性变化

doi:10.6023/A25120416

摘要/Abstract

以共价有机笼为模板合成限域钯团簇, 展现出独特多重类酶催化特性, 高效催化产生超氧阴离子($\text{O}_{\text{2}}^{\centerdot }$)与羟基自由基(•OH)等活性氧物种. 以能够保留天然膜复杂组成和结构特征的巨型质膜囊泡(GPMVs)为模型体系, 系统揭示了该限域纳米团簇产生的活性氧(ROS)对生物膜界面的调控作用. 研究发现, ROS优先作用于富含多不饱和脂肪酸的液态无序区, 引发空间选择性的脂质过氧化反应. 该过程显著重塑膜的物理化学性质: 一方面, 脂质过氧化产物促进膜相分离行为增强; 另一方面, 膜内部极性显著降低. 上述变化的本质源于脂质堆积方式与局域膜微环境的动态重构. 本研究阐明了ROS介导的脂质过氧化过程在空间维度上的非均一性特征, 揭示了脂质过氧化与膜极性及相分离行为之间的内在关联, 为基于膜物理化学性质精准调控的催化治疗策略提供了新的设计思路和理论依据.

关键词: 钯纳米粒子, 脂质过氧化, 活性氧, 膜极性

Confined palladium clusters are synthesized using covalent organic cages as templates, exhibiting unique multi- enzyme-like catalytic properties that can efficiently catalyze the production of reactive oxygen species, such as superoxide anion ($\text{O}_{\text{2}}^{\centerdot }$) and hydroxyl radical (•OH). Using giant plasma membrane vesicles (GPMVs) as a model system, which retain the complex composition and structural characteristics of natural membranes, the regulation of reactive oxygen species (ROS) generated by the confined nanoclusters at the biofilm interface was systematically revealed. Studies have shown that ROS preferentially act on the liquid-disordered regions rich in polyunsaturated fatty acids, triggering spatially selective lipid peroxidation. This process significantly reshapes the physical and chemical properties of the membrane: On the one hand, lipid peroxidation products promote the enhancement of membrane phase separation behavior; on the other hand, the internal polarity of the membrane is significantly reduced. The essence of these changes arises from the dynamic reconstruction of lipid accumulation and the local membrane microenvironment. This study clarified the heterogeneity of ROS-mediated lipid peroxidation in the spatial dimension and revealed the intrinsic relationship between lipid peroxidation, membrane polarity, and phase separation behavior. These findings provide a new design concept and theoretical basis for catalytic treatment strategies based on the precise regulation of membrane physicochemical properties.

Key words: palladium nanoparticles, lipid peroxidation, reactive oxygen species, membrane polarity

引用此文

马文杰, 汤佳栋, 王辰. 钯纳米团簇诱导脂质过氧化和膜物理特性变化[J]. 化学学报, 2026, 84(7): 1121-1128.

Wenjie Ma, Jiadong Tang, Chen Wang. Palladium Nanoclusters Induce Lipid Peroxidation and Alter Membrane Physical Properties[J]. Acta Chimica Sinica, 2026, 84(7): 1121-1128.

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图/表 7

图式1. PR高效产生ROS诱导脂质过氧化引起细胞膜极性变化和相分离

Scheme 1. The highly efficient production of ROS by PR induces lipid peroxidation, leading to changes in cell membrane polarity and phase separation

图式2. PR的合成路线

Scheme 2. The synthetic route of PR

图1. PR的表征. (a) PR的透射电子显微镜图像; (b) PR的选区高分辨率透射电子显微镜图像; (c) PR的扫描透射电子显微镜图像; (d~f) PR的快速傅里叶变换分析及相应的三维原子堆积模型和二维排列方式

Figure 1. Characterization of PR. (a) TEM imaging of PR; (b) Selected area HRTEM image of PR; (c) Scanning transmission electron microscopy (STEM) images of PR; (d~f) Fast Fourier transform (FFT) analysis and the corresponding 3D atomic packing model, and 2D arrangement of PR

图2. PR的类酶活性和生成ROS的种类. (a) PR协同催化示意图; (b)在PR和ROS清除剂存在下, oxTMB在652 nm处吸光度随时间变化; (c)在不同活性氧清除剂存在下oxTMB 2 min内652 nm处的吸光度强度变化; (d)不同浓度H2O2存在下oxTMB在652 nm处吸光度随时间的变化; (e) PR催化剂以H2O2为底物的Michaelis-Menten稳态动力学曲线. 反应体系包含0.5 mmol/L TMB、pH为6.5 4-羟乙基哌嗪乙磺酸(HEPES)缓冲液及不同浓度H2O2 (0~100 mmol/L). 红色曲线代表200 μg/mL PR存在下的动力学拟合, 黑色曲线为无PR对照; (f) PR催化剂以H2O2为底物的Lineweaver-Burk图

Figure 2. The enzyme-like activity of PR and the types of ROS generated. (a) Schematic diagram of PR synergistic catalysis; (b) The absorbance of oxTMB at 652 nm changes over time in the presence of PR and ROS scavengers; (c) The absorbance intensity of oxTMB at 652 nm changes within 2 min in the presence of different ROS scavengers; (d) The absorbance of oxTMB at 652 nm changes over time in the presence of different concentrations of H2O2; (e) The Michaelis-Menten steady-state kinetic curve of the PR catalyst with H2O2 as the substrate. The reaction system contained 0.5 mmol/L TMB, pH 6.5 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, and different concentrations of H2O2 (0~100 mmol/L). The red curve represents the kinetic fitting in the presence of 200 μg/mL PR, while the black curve serves as the control without PR; (f) Lineweaver-Burk plot of the PR catalyst with H2O2 as the substrate

图3. PR诱导脂质过氧化. (a)分别用空白组、PR、H2O2和PR＋H2O2处理GPMVs诱导其脂质过氧化的共聚焦激光扫描显微镜图像, 用C11-BODIPY进行染色, 其中氧化态为绿色荧光, 还原态为红色荧光. 比例尺为50 μm; (b)四组绿色荧光的相对荧光强度分析, ****, P<0.0001; ns: 无显著性差异

Figure 3. PR induced lipid peroxidation. (a) Confocal laser scanning microscope images (CLSM) of GPMVs induced lipid peroxidation were obtained for the blank group, PR, H₂O₂, and PR＋H₂O₂, respectively, and stained with C11-BODIPY. In these images, the oxidized state is represented by green fluorescence, while the reduced state is represented by red fluorescence. Scale bar=50 μm; (b) Relative fluorescence intensity analysis of the green fluorescence among four groups, ****, P<0.0001; ns: no significant difference

图4. 脂质过氧化优先发生在无序区且促进相分离. (a) C11-BODIPY标记的GPMVs在对照条件下或脂质过氧化后的代表性图像. DiD标记无序结构域. 比例尺为5 μm; (b)空白组及脂质过氧化处理后GPMVs发生相分离的比例统计. 数据来自10个独立实验中, 总样本数约50个

Figure 4. Lipid peroxidation preferentially occurrs in the disordered region and enhances phase separation. (a) Representative images of C11-BODIPY-labeled GPMVs under control conditions or after lipid peroxidation. DiD labels the disordered domains. Scale bar=5 μm; (b) Proportion of GPMVs exhibiting phase separation in the control group versus after lipid peroxidation treatment. Data are derived from 10 independent experiments, with a total of approximately 50 samples across all groups

图5. 脂质过氧化诱导细胞膜极性变化. (a)固定H2O2浓度为100 mmol/L, 改变PR (0~200 μg/mL)处理GPMVs后加入Laurdan检测其400~600 nm荧光光谱变化和(b)对应GP值. (c)固定PR浓度为100 μg/mL, 改变H2O2 (0~100 mmol/L)处理GPMVs后加入Laurdan检测其400~600 nm荧光光谱变化和(d)对应GP值

Figure 5. Lipid peroxidation induced changes in cell membrane polarity. (a) The concentration of H2O2 was fixed at 100 mmol/L. After treating the GPMVs with PR (0~200 μg/mL), Laurdan was added to detect changes in the 400~600 nm fluorescence spectrum and (b) the corresponding GP value; (c) The concentration of PR was fixed at 100 μg/mL, and GPMVs were treated with H2O2 (0~100 mmol/L). Laurdan was then added to detect changes in the 400~600 nm fluorescence spectra and (d) the corresponding GP values

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