Palladium Nanoclusters Induce Lipid Peroxidation and Alter Membrane Physical Properties

doi:10.6023/A25120416

Abstract

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

Cite this article

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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Fig. & Tab. 7

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

Scheme 2. The synthetic route of PR

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

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

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

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

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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