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Soft Matter · 2025 · IF 2.8

Modification of membrane properties using ionic liquids investigated with Langmuir monolayers and bilayers in vesicles

Manas Kumar Mandal,Shujiao Chen,Shuai Zhang,Qunhui Yuan,Wei Gan

Biocompatible and bioavailable ionic liquids (ILs) are generally used to modify the physicochemical properties of lipid monolayers and bilayers. Understanding the influence of ILs on lipid properties and the molecular level mechanism is crucial for applying ILs in lipid membrane modifications. Here the modification of a lipid membrane composed of 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG) and cholesterol using alkyl methyl imidazolium-based ILs [Cnmim]Cl with varied alkyl chains (n = 4, 6, 8 and 10) was investigated. Langmuir monolayers were used to evaluate the influence of the ILs on the rigidity and robustness of the membranes. Then, selected compositions were used to prepare small unilamellar vesicles (SUVs) as nanocarriers. A small amphiphilic molecule (4-(4-diethylaminostyry)-1-methyl-pyridinium iodide, D289) was used as a probe to investigate the loading capability and encapsulation efficiency of the SUVs. The permeability of the lipid membrane to small molecules was also evaluated using second harmonic generation spectroscopy analysis. The different effects of the ILs with increasing chain length imposed on the membranes were compared and analyzed.

CAS / MDL: 171058-18-7 79917-90-1
研究领域: 生物物理学 · 药剂学
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Membranes · 2023 ·Vol. 13 ·期 1 ·61 · IF 4.2

The Interaction of Anthracycline Based Quinone-Chelators with Model Lipid Membranes: 1H NMR and MD Study

Olga Yu. Selyutina,Anna V. Mastova,Nikolay E. Polyakov

Anthracycline antibiotics, e.g., doxorubicin, daunomycin, and other anthraquinones, are an important family of antitumor agents widely used in chemotherapy, which is currently the principal method for treating many malignancies. Thus, development of improved antitumor drugs with enhanced efficacy remains a high priority. Interaction of anthraquinone-based anticancer drugs with cell membranes attracts significant attention due to its importance in the eventual overcoming of multidrug resistance (MDR). The use of drugs able to accumulate in the cell membrane is one of the possible ways of overcoming MDR. In the present work, the aspects of interaction of anthraquinone 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione) (Q1) with a model membrane were studied by means of NMR and molecular dynamics simulations. A fundamental shortcoming of anthracycline antibiotics is their high cardiotoxicity caused by reactive oxygen species (ROS). The important feature of Q1 is its ability to chelate transition metal ions responsible for ROS generation in vivo. In the present study, we have shown that Q1 and its chelating complexes penetrated into the lipid membrane and were located in the hydrophobic part of the bilayer near the bilayer surface. The chelate complex formation of Q1 with metal ions increased its penetration ability. In addition, it was found that the interaction of Q1 with lipid molecules could influence lipid mobility in the bilayer. The obtained results have an impact on the understanding of molecular mechanisms of Q1 biological activity.Keywords:anthraquinones;NMR;molecular dynamics;lipid membranes

CAS / MDL: 60-33-3
研究领域: 药理学 · 生物物理学
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ANALYST · 2016 ·Vol. 141 ·期 15 ·4676-4684 · IF 4.033

Monitoring drug–lipid membrane interactions via a molecular rotor probe

Qinqin Xu,Tao Zhao,Zhihua Sun

Molecular rotors are fluorescent molecules with a viscosity-sensitive fluorescence quantum yield that are often used to measure viscosity changes in biological membranes. Herein, we report the use of a lipophilic molecular rotor probe to monitor the interactions between the local anesthetic tetracaine (TTC) and small unilamellar vesicles (SUVs) in a label-free manner. The probe was developed by modifying the fluorescent molecular rotor CCVJ with an amphiphilic anchor group that enables adequate integration of the rotor group into the hydrophobic core of lipid bilayers. The temperature-dependent profile of the quantum yield of the probe clearly exhibited the subtransition, pretransition and main phase transition of the lipid bilayers as drastic changes in the activation energies. The temperature-TTC phase diagrams were determined based on an Arrhenius fitting. The results show that TTC has a significant chain ordering effect on liquid-crystalline phase lipids compared to solid-gel phase lipids, especially subgel phase lipids. A TTC-induced interdigitated gel (LβI) phase appeared at the pretransition temperature. The LβI phase spread both its ends in a TTC-dependent fashion, and the low-temperature end merged to the subtransition at a TTC concentration of 25 mM. Adding cholesterol (CHOL) to the SUVs stabilizes the LβI phase and reduces the insertion of TTC into the bilayers. The paper demonstrates that our method is highly sensitive to the microenvironment of the lipid membrane, providing a facile and efficient new tool to study drug–membrane interactions. Also, molecular rotors may potentially be exploited as screen probes for drug development and analysis.

研究领域: 生物物理学 · 药理学
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Nanoscale · 2019 ·Vol. 11 ·期 20 ·10080-10087 · IF 6.97

Correlation between the translational and rotational diffusion of rod-shaped nanocargo on a lipid membrane revealed by single-particle tracking

Liangna He,Yiliang Li,Lin Wei,Zhongju Ye,Hua Liu,Lehui Xiao

Revealing the diffusion dynamics of nanoparticles on a lipid membrane plays an important role in a better understanding of the cellular translocation process and provides a theoretical basis for the rational design of delivery cargo. However, most studies focus on the investigation of the positional fluctuations of the nanocargo on the fluidic membrane, ignoring the contribution from orientational variation. In particular, less is known about the correlation between the rotational freedom and translational movability of a particle surveying a lipid membrane. In this work, the ligand–receptor interaction (by using streptavidin (SA) and biotin as the model)-modulated diffusion dynamics of rod-shaped nanocargo (i.e., gold nanorods, GNRs) on an artificial lipid membrane was explored with dark-field (DF) optical microscopy. A correlation between translational and rotational motion was observed whereby the freedom of rotational motion could be released intermittently. The conformational entropy release is usually associated with the promotion of translational diffusion, where large step surveying on the lipid membrane takes place subsequently. These new messages might afford valuable kinetic information for the design of nanocargo with appropriate surface functionality to achieve satisfactory cellular uptake efficiency.

研究领域: 生物物理学 · 细胞生物学
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JOURNAL OF PHYSICAL CHEMISTRY B · 2019 · IF 2.923

pH/Redox-Controlled Interaction between Lipid Membranes and Peptide Derivatives with a “Helmet”

Mengya Li,Sijia Wang,Jun Xu,Shouhong Xu,Honglai Liu

How to reduce the cytotoxicity of antitumor peptides to normal cells remains an ongoing challenge. Here, we designed a pH/redox-responsive supramolecular structure (Pep-V⊂P-PEG) composed of a peptide modified with viologen (Pep-V) and polyethylene glycol bearing pillar[5]arene (P-PEG) as a “helmet”. By shielding the hydrophobic moiety of the peptide derivative with pillar[5]arene via host–guest interactions, its disruption on normal cells can be effectively reduced. At acidic pH, the supramolecular structure can selectively adsorb onto negatively charged lipid membranes because of electrostatic interactions. Owing to redox responsiveness of the viologen group, Pep-V could be separated from P-PEG after the addition of reductants and inserted into lipid bilayers, which leads to membrane disruption. Cargo leakage of liposome models was investigated to understand Pep-V⊂P-PEG-induced liposomal membrane disruption under different pH values and redox conditions. Results showed that Pep-V⊂P-PEG caused almost no cargo leakage from (1,2-dipalmitoyl-sn-glycerol-3-phosphocholine) liposomes at pH 7.4 but significant leakage from negatively charged (1,2-dipalmitoyl-sn-glycerol-3-phospho-(1-rac-glyerol)) liposomes at pH 5.0 under a reducing environment. Pep-V⊂P-PEG displayed low destructive effects on mimic normal cells and significant disruption to mimic tumor cells when exposed to a reducing environment that is expected to be a potential antitumor agent.

CAS / MDL: 77-86-1
研究领域: 生物化学 · 药理学
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Food Chemistry-X · 2023 · IF 6.1

Application of electronic tongue in umami detection and soy sauce refining process

Jianan Zhang,Xuechen Zhao,Lufang Li,Wen Chen,Qiangzhong Zhao,Guowan Su,Mouming Zhao

The article systematically investigated the response behaviors of lipid-film equipped umami taste sensor to various umami compounds, including typical umami substances (umami amino acids, GMP, IMP, disodium succinate) and novel umami chemicals (umami peptide and Amadori rearrangement product of umami amino acid). The umami taste sensor has great specificity to all umami substances. Relationships between output values and concentrations of umami substances in certain ranges were consistent with Weber-Fechner law. The umami synergistic effect detected by the sensor was in great agreement with human sensory results as well, fitting logarithm model. Moreover, the taste profile mixing model of raw soy sauce was established using five different taste sensors and principal component analysis, realizing the simplification of soy sauce blending and acceleration of the soy sauce refining process. Thus, flexible design of the experimental procedure and multi-analysis of the sensor data is essential.

研究领域: 食品科学 · 生物传感技术
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LANGMUIR · 2019 · IF 3.683

Understanding the Synergic Mechanism of Weak Interactions between Graphene Oxide and Lipid Membrane Leading to the Extraction of Lipids

Xiaofei Zhang,Fengjuan Cao,Lie Wu,Xiue Jiang

Revealing how weak forces interact synergistically to induce differences in nanobio effects is critical to understanding the nature of the nanobio interface. Herein, graphene oxide (GO) and a lipid membrane are selected as a nanobio model, and interaction forces at the GO–biomembrane interface are modulated by varying the amounts and species of oxygenated functional groups on the surface of GO. A synergic mechanism of interfacial interaction forces is investigated by a combination of surface-enhanced infrared absorption (SEIRA) spectroscopy, confocal laser scanning microscopy (CLSM), and electrochemical impedance spectroscopy (EIS). The results reveal that after balancing with electrostatic repulsion, the moderate attraction between GO and lipid headgroups (such as electrostatic and/or hydrophobic interactions) is most favorable for lipid extraction, whereas lipid extraction is inhibited under an attraction that is too strong or too weak. Under moderate attraction between GO and the headgroups of lipids, the appropriate degree of rotation freedom is maintained for GO, which is beneficial to the hydrogen-bonding interaction between the C═O group in the phosphatide hydrophobic region and GO, thus triggering the insertion of GO into the lipid alkyl chain region, resulting in the rapid and significant extraction of lipids. Our results have important guiding significance for how to reveal the synergistic mechanism of weak interactions at the nanobio interface.

CAS / MDL: 7782-42-5
研究领域: 纳米生物学 · 生物物理学
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Chemical Science · 2018 ·Vol. 10 ·期 5 ·1351-1359 · IF 9.063

Single-particle tracking discloses binding-mediated rocking diffusion of rod-shaped biological particles on lipid membranes

Zhongju Ye,Hua Liu,Fuyan Wang,Xin Wang,Lin Wei,Lehui Xiao

It has been demonstrated that rod-shaped particles can achieve a high translocation efficiency for gene and drug delivery in biological samples. Previous theoretical calculations also confirmed that rod-shaped particles display higher diffusivity than their spherical counterparts in biological porous media. Understanding the diffusion dynamics of biological and non-biological rod-shaped particles in biological solutions as well as close to the lipid membrane is therefore fundamentally significant for the rational design of efficient cargos. With dark-field optical microscopy, the translational and three-dimensional (3D) orientational diffusion dynamics of individual rod-shaped particles (i.e., E. coli and upconversion microrods, UCMRs) in phosphate buffered saline (PBS) and on the lipid membrane are tracked at the single-particle level. In the buffer solution, faster rotation of E. coli in the z direction was observed even though its dynamics in the x–y plane is comparable with that of UCMRs. Interestingly, on the lipid membrane, distinct from the confined motion of UCMRs, anomalous rocking diffusion was observed, which might facilitate the subsequent survey of stronger association sites on the two-dimensional (2D) surface. These results would afford deep insight into the better understanding of the translocation mechanism by using rod-shaped particles as a delivery cargo in biological samples.

CAS / MDL: 13476-05-6 13494-98-9
研究领域: 生物物理学 · 药物递送 · 细胞生物学
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SCIENCE OF THE TOTAL ENVIRONMENT · 2023 · IF 9.8

Cytotoxicity and hemolysis of rare earth ions and nanoscale/bulk oxides (La, Gd, and Yb): Interaction with lipid membranes and protein corona formation

Yiping Feng,Jingyi Wu,Haijian Lu,Wenhao Lao,Hongda Zhan,Longyong Lin,Guoguang Liu,Yirong Deng

The widespread application of rare earth elements (REEs) has raised concerns about their potential release into the environment and subsequent ingestion by humans. Therefore, it is essential to evaluate the cytotoxicity of REEs. Here, we investigated the interactions between three typical REEs (La, Gd, and Yb) ions as well as their nanometer/μm-sized oxides and red blood cells (RBCs), a plausible contact target for nanoparticles when they enter the bloodstream. Hemolysis of REEs at 50–2000 μmol L −1 was examined to simulate their cytotoxicity under medical or occupational exposure. We found that the hemolysis due to the exposure of REEs was highly dependent on their concentration, and the cytotoxicity followed the order of La 3+  > Gd 3+  > Yb 3+ . The cytotoxicity of REE ions (REIs) is higher than REE oxides (REOs), while nanometer-sized REO caused more hemolysis than that μm-sized REO. The production of reactive oxygen species (ROS), ROS quenching experiment, as well as the detection of lipid peroxidation, confirmed that REEs causes cell membrane rupture by ROS-related chemical oxidation. In addition, we found that the formation of a protein corona on REEs increased the steric repulsion between REEs and cell membranes, hence mitigating the cytotoxicity of REEs. The theoretical simulation indicated the favorable interaction of REEs with phospholipids and proteins. Therefore, our findings provide a mechanistic explanation for the cytotoxicity of REEs to RBCs once they have entered the blood circulation system of organisms.

研究领域: 毒理学 · 纳米技术 · 生物医学工程 · 环境科学
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NEW JOURNAL OF CHEMISTRY · 2022 ·Vol. 46 ·期 16 ·7748-7757 · IF 3.925

Structural effects of zinc on phosphatidylserine-containing lipid membranes: kinetic analysis of membrane reorganization

Danling Cheng,Hewen Li,Shipeng Hu,Tao Zhao

The interaction between metal ions and phospholipids plays an essential role in cellular signal transduction, oxidative lipid damage and other biological processes. Herein, we report fluorescence microscopy analysis of the interaction between Zn2+ on planar supported lipid bilayers (SLBs), as model membranes. The results show that Zn2+ interacts with palmitoyl oleoyl phosphatidylserine (POPS), a negatively charged phospholipid, in palmitoyl oleoyl phosphatidylcholine (POPC) SLBs, which leads to significant structural reorganization of the bilayer. Upon Zn2+ binding, the formation of bilayer stacks was observed, which led to the subsequent disruption of the membrane. The kinetics of bilayer stack formation could be described with a characteristic sigmoidal profile and a three-stage mechanism consisting of a lag phase for initial nucleation (formation of stable nuclei), a subsequent exponential phase for growth (growth of nuclei to bilayer stacks) and a final stationary phase was proposed. The lag time reduced in an exponential fashion with increasing Zn2+ concentration and the lag phase could be essentially eliminated in SLBs with high POPS content. Moreover, a linear dependency of the apparent first-order rate constant for bilayer stack growth on Zn2+ concentration was established. Besides, the equilibrium dissociation constants for Zn2+-membrane interaction were calculated and the affinity between Zn2+ and SLBs increased with an increase in the POPS content in the membrane. These results have important implications in general understanding of ion-mediated malformations of cell membranes and cell fusion. Also, this work provides an interesting in vitro system for studying metal ions interacting with biomembranes.

研究领域: 生物物理 · 细胞生物学 · 膜科学
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ANALYTICAL CHEMISTRY · 2018 · IF 6.042

Electrochemical Impedance Spectroscopy for Real-Time Detection of Lipid Membrane Damage Based on a Porous Self-Assembly Monolayer Support

Meng Zhang,Qingyu Zhai,Liping Wan,Li Chen,Yu Peng,Chunyan Deng,Juan Xiang,Jiawei Yan

Layer-by-layer dissolution and permeable pore formation are two typical membrane damage pathways, which induce membrane function disorder and result in serious disease, such as Alzheimer’s disease, Keshan disease, Sickle-cell disease, and so on. To effectively distinguish and sensitively monitor these two typical membrane damage pathways, a facile electrochemical impedance strategy was developed on a porous self-assembly monolayer (pSAM) supported bilayer lipid membrane (BLM). The pSAM was prepared by selectively electrochemical reductive desorption of the mercaptopropionic acid in a mixed mercaptopropionic acid/11-mercaptoundecanoic acid self-assembled monolayer, which created plenty of nanopores with tens of nanometers in diameter and several nanometers in height (defined as inner-pores). The ultralow aspect ratio of the inner-pores was advantageous to the mass transfer of electrochemical probe [Fe(CN)6]3–/4–, simplifying the equivalent electric circuit for electrochemical impedance spectroscopy analysis at the electrode/membrane interface. [Fe(CN)6]3–/4– transferring from the bulk solution into the inner-pore induce significant changes of the interfacial impedance properties, improving the detection sensitivity. Based on these, the different membrane damage pathways were effectively distinguished and sensitively monitored with the normalized resistance-capacitance changes of inner-pore-related parameters including the electrolyte resistance within the pore length (Rpore) and the metal/inner-pore interfacial capacitance (Cpore) and the charge-transfer resistance (Rct-in) at the metal/inner-pore interface.

研究领域: 生物物理学 · 分析化学 · 医学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

An efficient metal–organic framework-based drug delivery platform for synergistic antibacterial activity and osteogenesis

Yunhui Si,Huanyao Liu,Mengsha Li,Xuzhou Jiang,Hongying Yu,Dongbai Sun

Bone implants for clinical application should be endowed with antibacterial activity , biocompatibility, and even osteogenesis-promoting properties. In this work, metal–organic framework (MOF) based drug delivery platform was used to modify titanium implants for improved clinical applicability. Methyl [email protected] Imidazolate Framework-8 ( [email protected] ) was immobilized on the polydopamine (PDA) modified titanium. The sustainable release of the Zn 2+ and MV causes substantial oxidative damage to Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The increased reactive oxygen species (ROS) significantly up-regulates the expression of oxidative stress and DNA damage response genes. Meanwhile, the structural disruption of lipid membranes caused by the ROS, the damage caused by Zinc active sites and the damage accelerated by the MV are both involved in inhibiting bacterial proliferation. The up-regulated expression of the osteogenic-related genes and proteins indicated that the [email protected] could effectively promote the osteogenic differentiation of the human bone mesenchymal stem cells (hBMSCs). RNA sequencing and Western blotting analysis revealed that the [email protected] coating activates the canonical Wnt/β-catenin signaling pathway through the regulation of tumor necrosis factor (TNF) pathway, thereby promoting the osteogenic differentiation of the hBMSCs. This work demonstrates a promising application of the MOF-based drug delivery platform in bone tissue engineering.

CAS / MDL: 9002-93-1
研究领域: 生物材料 · 药物递送系统 · 组织工程 · 生物医学工程 · 微生物学 · 细胞生物学
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