Publications (17)52.96 Total impact
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Article: Bacteria-mediated in vivo delivery of quantum dots into solid tumor.
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ABSTRACT: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.Biochemical and Biophysical Research Communications 08/2012; 425(4):769-74. · 2.48 Impact Factor -
Article: Effect of Aβ1-−40on membrane permeability and intracellular free Ca2+ of nerve cells
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ABSTRACT: The effects of soluble and fibrillar Aβ1−40 on membrane permeability and intracellular free Ca2+ of nerve cells were investigated by the laser confocal microscopy. Results indicate that: i) Effects of soluble and fibrillar Aβ1−40 on cell membrane permeability are both concentration-dependent. Soluble Aβ1−40increases membrane permeability only at concentration of 3 μmol/L, while the toxic effect of fibrillar Aβ1−40 is much stronger, its evident effect begins from 1 μmol/L. When its concentration rose to 3 μmol/L, not only the membrane permeability increased, but also the nuclear membrane broke seriously, ii) Both soluble and fibrillar Aβ1−40 at high concentrations increased the intracellular free Ca2+, and the increased amplitudes are concentration-dependent. However, the fibrillar one induces the increase of intracellular Ca2+ much quicker and synchronously. These results indicate that some correlation exists between the neurotoxicity of high concentration soluble and fibrillar Aβ1−40 and the change of physico-chemical properties and intracellular Ca ion imbalance. Keywordssoluble and fibrillar Aβ1−40 -membrane permeability-intracellular calciumChinese Science Bulletin 04/2012; 48(10):974-978. · 1.32 Impact Factor -
Article: Interaction of HIV-1 fusion peptide and its mutant with lipid membrane
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ABSTRACT: HIVWT and HIVV2E represent the 23 amino acids fusion peptide of HIV-1 gp41 N terminus and its position 2 mutant (Val→Glu). We have studied the structure-function relationship of HIVWT and HIVV2E when they interact with acidic and neutral lipid membranes. The results show that HIVWT and HIVV2E have the same conformational characteristics and tendencies of conformational transition but definitely different functions: HIVWT destabilizes membrane and induces fusion by adopting predominant α-helix conformation when interacting with acidic POPG membrane, its phenylalanine residues can penetrate into the hydrophobic core of POPG bilayer; HIVV2E also adopts predominant α-helix when interacting with POPG membrane, but it cannot destabilize POPG membrane and induce fusion, the phenylalanine residues of it are located near the surface of POPG bilayer. HIVWT and HIVV2E both adopt predominant β-sheet conformation to interact with neutral POPC membrane, and cannot destabilize POPC membrane and induce fusion, the position of phenylalanine residues of both HIVWT and HIVV2E are close to the surface of POPC bilayer. These results demonstrate that the N terminal hydrophobicity of fusion peptide and the secondary structure when interacting with lipid membrane play important roles for fusion peptide exerting its function.Chinese Science Bulletin 04/2012; 45(9):819-825. · 1.32 Impact Factor -
Article: Bionanoprobes with excellent two-photon-sensitized Eu3+ luminescence properties for live cell imaging.
Chemistry 08/2010; 16(29):8647-51. · 5.93 Impact Factor -
Article: Polyvalent lactose-quantum dot conjugate for fluorescent labeling of live leukocytes.
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ABSTRACT: Oligosaccharides play crucial roles in many biorecognition processes by the so-called "cluster glycosidic effect". We here report a facile synthesis of lactose-CdSeS/ZnS quantum dot conjugate (Lac-QDs) by use of 1-thiol-beta-D-lactose via ligand exchange, which exhibits significantly high affinity and specificity to leukocytes in contrast to the monovalent lactose. Structural analyses indicate that there are about 132 lactosyl molecules assembled on single QDs and the hydrodynamic diameter is small, close to 8.2 nm. Further, Lac-QDs display good fluorescence and physicochemical stability in physiological conditions, as well as extremely low cytotoxicity. These properties facilitate the use of Lac-QDs in fluorescent labeling of live leukocytes.Langmuir 06/2010; 26(11):8534-9. · 4.19 Impact Factor -
Article: The role of calcium ions in the interactions of PrP106-126 amide with model membranes.
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ABSTRACT: In this work, we investigated the interactions of PrP106-126 amide with 1-palmitoyl-2-oleoyl-3-phosphocholine (POPC) and POPC/bovine brain sphingomyelin (BSM) membranes in the presence of calcium ions by in situ time-lapse atomic force microscopy (AFM) and circular dichroism (CD). The CD results show that Ca(2+) has no obvious effects on the random coil conformation of PrP106-126 amide. The tapping mode AFM results demonstrate that electrostatic interaction decreases the measured heights of supported lipid bilayers (SLBs) in HBS-Ca(2+) solution. Electrostatic interaction analysis also can be used to determine the applied force in liquid tapping mode AFM. The interactions of PrP106-126 amide with membranes by AFM demonstrate the following: (i) Ca(2+) inhibits the interaction of PrP106-126 amide with POPC lipid and (ii) the co-interaction between Ca(2+) and BSM increases the poration ability of PrP106-126 amide. These results imply that the main role of Ca(2+) in the interactions of PrP106-126 amide with membranes is changing the surface properties of the membranes.Colloids and surfaces. B, Biointerfaces 05/2010; 77(1):40-6. · 2.60 Impact Factor -
Article: A designed beta-hairpin forming peptide undergoes a consecutive stepwise process for self-assembly into nanofibrils.
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ABSTRACT: We used a de novo designed, beta-hairpin forming T1 peptide as a model to investigate the kinetics of peptide fibrogenesis by a combination of light scattering (LS), circular dichroism (CD), fluorescence, and atomic force microscopy (AFM). The results demonstrate that the T1 fibrogenesis undergoes a consecutive stepwise process, with a high degree of cooperation, presenting sigmoidal time-courses of the peptide aggregation, the subsequent conformational conversion of the backbone, and the peptide sidechains' rearrangement. We suggest that the conformational conversion was initiated after the peptide aggregates reach a dimensional size threshold, which could be a key step in the formation of beta-structural nuclei that catalyze the subsequent reactions. Furthermore, besides triggering the peptide aggregation, the interactions between the peptide sidechains predominately facilitate the regular alignment of the peptide molecules and the formation of a well-defined suprastructure. This work provides an insight of the hierarchical self-assembly of beta-hairpin forming peptides. It is helpful for designing beta-structural peptides for self-assembly into nanowires, which would have potential applications in the construction of nano-materials.Protein and Peptide Letters 12/2009; 17(4):410-5. · 1.94 Impact Factor -
Article: A facile synthesis of small-sized, highly photoluminescent, and monodisperse CdSeS QD/SiO(2) for live cell imaging.
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ABSTRACT: In recent years, silica coating has been extensively investigated to fabricate the biocompatible interface of quantum dots (QDs) for biomedical applications. We here describe a facile and efficient method of synthesizing high-quality silica-coated CdSeS QDs (CdSeS QD/SiO(2)), where an immediate photoluminescence-favorable microenvironment is first created by assembling amphiphilic molecules around the CdSeS core, and a thin silica shell is further introduced to protect this hydrophobic interlayer. The prepared CdSeS QD/SiO(2) exhibits excellent properties such as good water solubility, low cytotoxicity, and high quantum yield (QY, up to 0.49) as well as the resistance of photobleaching in aqueous solution. Also, the CdSeS QD/SiO(2) nanoparticles homogeneously comprise single CdSeS cores and hold a comparatively small size up to about 11 nm in diameter. Particularly, this method leads to a significant increase in QY as compared to the uncoated CdSeS QDs ( approximately 109% of the initial QY), though only thin silica shells formed in the CdSeS QD/SiO(2) structure. By coupling with folic acids, the CdSeS QD/SiO(2) conjugates were successfully used for tumor cell labeling. Our results demonstrated a robust hydrophobic QDs-based approach for preparing highly photoluminescent, biocompatible QD/SiO(2) through creation of a stable hydrophobic interlayer surrounding the QD cores, which could be also suitable for silica coating of other kinds of hydrophobic nanoparticles.Langmuir 10/2009; 25(20):12250-5. · 4.19 Impact Factor -
Article: Effects of lipid composition and phase on the membrane interaction of the prion peptide 106-126 amide.
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ABSTRACT: Lipid rafts are specialized liquid-ordered (L(o)) phases of the cell membrane that are enriched in sphingolipids and cholesterol (Chl), and surrounded by a liquid-disordered (L(d)) phase enriched in glycerophospholipids. Lipid rafts are involved in the generation of pathological forms of proteins that are associated with neurodegenerative diseases. To investigate the effects of lipid composition and phase on the generation of pathological forms of proteins, we constructed an L(d)-gel phase-separated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/sphingomyelin (from bovine brain (BSM))-supported lipid bilayer (SLB) and an L(d)-L(o) phase-separated POPC/BSM/Chl SLB. We used in situ time-lapse atomic force microscopy to study the interactions between these SLBs and the prion peptide K(106)TNMKHMAGAAAAGAVVGGLG(126) (PrP106-126) amide, numbered according to the human prion-peptide sequence. Our results show that: 1), with the presence of BSM in the L(d) phase, the PrP106-126 amide induces fully penetrated porations in the L(d) phase of POPC/BSM SLB and POPC/BSM/Chl SLB; 2), with the presence of both BSM and Chl in the L(d) phase, the PrP106-126 amide induces the disintegration of the L(d) phase of POPC/BSM/Chl SLB; and 3), with the presence of both BSM and Chl in the L(o) phase, PrP106-126 amide induces membrane thinning in the L(o) phase of POPC/BSM/Chl SLB. These results provide comprehensive insight into the process by which the PrP106-126 amide interacts with lipid membranes.Biophysical Journal 07/2009; 96(11):4610-21. · 3.65 Impact Factor -
Article: PrP106-126 peptide disrupts lipid membranes: influence of C-terminal amidation.
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ABSTRACT: PrP106-126 is located within the important domain concerning membrane related conformational conversion of human Prion protein (from cellular isoform PrP(C) to scrapie isoform PrP(Sc)). Recent advances reveal that the pathological and physicochemical properties of PrP106-126 peptide are very sensitive to its N-terminal amidation, however, the detailed mechanism remains unclear. In this work, we studied the interactions of the PrP106-126 isoforms (PrP106-126(CONH2) and PrP106-126(COOH)) with the neutral lipid bilayers by atomic force microscopy, surface plasmon resonance and fluorescence spectroscopy. The membrane structures were disturbed by the two isoforms in a similarly stepwise process. The distinct morphological changes of the membrane were characterized by formation of semi-penetrated defects and sigmoidal growth of flat high-rise domains on the supported lipid bilayers. However, PrP106-126(COOH) displayed a higher peptide-lipid binding affinity than PrP106-126(CONH2) (approximately 2.9 times) and facilitated the peptide-lipid interactions by shortening the lag time. These results indicate that the C-terminal amidation may influence the pathological actions of PrP106-126 by lowering the interaction potentials with lipid membranes.Biochemical and Biophysical Research Communications 01/2009; 379(2):298-303. · 2.48 Impact Factor -
Article: Parallel-oriented fibrogenesis of a beta-sheet forming peptide on supported lipid bilayers.
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ABSTRACT: Peptide self-assembly on substrates is currently an intensively studied topic that provides a promising strategy for fabrication of soft materials and is also important for revealing the surface chemistry of amyloidogenic proteins that aggregate on cell membranes. We investigated the fibrogenesis of a beta-sheet forming peptide Abeta(26-35) on supported lipid bilayers (SLBs) by in situ atomic force microscopy (AFM), circular dichroism (CD), and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. The results show that the Abeta(26-35) nanofilaments' growth is oriented to a specific direction and formed a highly ordered, large-scale, parallel-oriented surface pattern on membranes. The parallel-oriented fibrogenesis of Abeta(26-35) was able to occur on different lipid membranes rather than on solid substrates. It implies that the parallel-oriented fibrogenesis was associated with the distinct properties of lipid membranes, such as the fluid nature of lipid molecules on membranes. The membrane fluidity may allow the peptide assemblies to float at the water-membrane interface and easily orient to an energetically favorable state. These results provide an insight into the surface chemistry of peptide self-assembly on lipid membranes and highlight a possible way to fabricate supramolecular architectures on the surface of soft materials.The Journal of Physical Chemistry B 08/2008; 112(30):8950-4. · 3.70 Impact Factor -
Article: Ganglioside GM1 binding the N-terminus of amyloid precursor protein.
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ABSTRACT: Secreted amyloid precursor protein (APPs) plays a role in several neuronal functions, including the promotion of synaptogenesis, neurite outgrowth and neuroprotection. Previous study has demonstrated that ganglioside GM1 inhibits the secretion of APPs; however the underlying mechanism remains unknown. Here we reported that GM1 can bind cellular full length APP and APPs secreted from APP(695) stably-transfected SH-SY5Y cells. To characterize the GM1-APP interaction further, we expressed and purified recombinant fragments of the N-terminal APP. Immunoprecipitation experiments revealed that GM1 was able to bind the recombinant APP(18-81) fragment. Moreover, the synthetic peptide APP(52-81) could inhibit the binding. Therefore, the binding site for GM1 appears to be located within residues 52-81 of APP. Furthermore, we found that only GM1, but not GD1a, GT1b and ceramide, binds APP-N-terminus, indicating that the specific binding depends on the sugar moiety of GM1. Fluorescent studies revealed a decrease in the intrinsic fluorescence intensity of the APP(52-81) peptide in phosphatidylcholine (PC)/GM1 vesicles. By using FTIR techniques, we found that the major secondary structure of the APP(52-81) peptide was altered in PC/GM1 vesicles. Our results demonstrate that GM1 binds the N-terminus of APP and induces a conformational change. These findings suggest that secreted APP is decreased by membrane GM1 binding to its precursor protein and provide a possible molecular mechanism to explain the involvement of GM1 in APP proteolysis and pathogenesis of Alzheimer's disease.Neurobiology of aging 01/2008; 30(8):1245-53. · 5.94 Impact Factor -
Article: PrP106-126 amide causes the semi-penetrated poration in the supported lipid bilayers.
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ABSTRACT: A major hallmark of prion diseases is the cerebral amyloid accumulation of the pathogenic PrP(Sc), an abnormally misfolded, protease-resistant, and beta-sheet rich protein. PrP106-126 is the key domain responsible for the conformational conversion and aggregation of PrP. It shares important physicochemical characteristics with PrP(Sc) and presents similar neurotoxicity as PrP(Sc). By combination of fluorescence polarization, dye release assay and in situ time-lapse atomic force microscopy (AFM), we investigated the PrP106-126 amide interacting with the large unilamellar vesicles (LUVs) and the supported lipid bilayers (SLBs). The results suggest that the interactions involve a poration-mediated process: firstly, the peptide binding results in the formation of pores in the membranes, which penetrate only half of the membranes; subsequently, PrP106-126 amide undergoes the poration-mediated diffusion in the SLBs, represented by the formation and expansion of the flat high-rise domains (FHDs). The possible mechanisms of the interactions between PrP106-126 amide and lipid membranes are proposed based on our observations.Biochimica et Biophysica Acta 07/2007; 1768(6):1420-9. · 4.66 Impact Factor -
Article: One-dimensional self-assembly of a rational designed beta-structure peptide.
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ABSTRACT: Fabricating various nanostructures based on the self-assembly of diverse biological molecules is now of great interest to the field of bionanotechnology. In this study, we report a de novo designed peptide (T1) with a preferential beta-hairpin forming property that can spontaneously assemble into nanofibrils in ultrapure water. The nanofibrils assembled by T1 could grow up to tens of microns in length with a left-handed helical twist and an average height of 4.9 +/- 0.9 nm. Moreover, protofilaments and nucleus structures both with a similar height of 1.4 +/- 0.2 nm were observed during fibrilization as well as via sonication of the mature nanofibrils. A typical conformational transition from random coil to beta-structure was observed in association with the fibrilization. Molecular modeling of T1 assemblies displayed that the beta-hairpin molecules organize in a parallel fashion in which the beta-strands align in an antiparallel fashion and each adjoining beta-strand runs left-handed twist at about 2.9 degrees with respect to the one located before it along the fibrillar axis. It also revealed that the maximum thickness of the assembly intermediate, the helical tape structure, is about 1.4 nm and four tapes can further assemble into a fibril with a diameter of about 4.1 nm. Taken together the results obtained by AFM, CD, and molecular modeling, T1 fibrilization probably undergoes a hierarchy approach, in which the aromatic stacking and the electrostatic interactions between the assembled structures are most likely the two major factors directing the one-dimensional self-assembly. Based on these studies, we propose T1 can be used as a model peptide to investigate the beta-sheet based self-assembly process and could be a potential bioorganic template to develop functional materials.Biopolymers 06/2007; 86(1):23-31. · 2.87 Impact Factor -
Article: Separation and analysis of the soluble trimer of Aβ1–40 and its effects on the rise in intracellular calcium
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ABSTRACT: The oligomers of Aβ1–40 peptide in PBS buffer solution were analyzed by SEC and native PAGE, and the trimer of Aβ1–40 was also isolated by SEC. In addition, the effects of the soluble Aβ1–40 trimer on intracellular free calcium (Ca2+) balance of hippocampal neurons of postnatal rats were investigated by fluorescence microscopy. The experimental results indicated that Aβ1–40 peptide existed in the form of low molecular weight oligomers in 0.231 mmol/L fresh Aβ1–40 solution (20 mmol/L sodium phosphate buffer, pH 7.4, 0.02% sodium azide) within 24 h and the soluble trimer was the most abundant species. Both the trimeric and the fibrillar Aβ1–40 were able to increase the intracellular Ca2+ concentration, but the Aβ1–40 trimer caused a gradual rise and the potential was also stronger than that of the fibrils at the same concentration. In addition there were different response modes for trimeric and fibrillar Aβ1–40, meaning that there are different mechanisms of increase in intracellular Ca2+ caused by Aβ1–40.Chinese Science Bulletin 03/2006; 51(7):830-838. · 1.32 Impact Factor -
Article: Humanin peptides block calcium influx of rat hippocampal neurons by altering fibrogenesis of Abeta(1-40).
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ABSTRACT: Humanin peptides (including HN, HNG and other mutants) were reported previously that antagonize neurotoxicity caused by various familial Alzheimer's disease (FAD) genes and Abeta derivatives. Herein, we describe the aggregation dynamics and the representative morphological characteristics of Abeta(1-40) after different time of addition humanin peptides, which revealed that (a) the interactions of both HN and HNG with Abeta(1-40) induced quick and significant increase of light-scattering intensity, and (b) HNG also caused obvious morphological alteration from fibrillary to amorphous. In the meantime, the experiments also revealed that the interaction of HNG with Abeta(1-40) could decrease Abeta(1-40)-induced calcium rise, an initial event accompanying Abeta(1-40)-induced apoptosis of cultured neurons. Our results indicate that HNG can protect neurons by altering Abeta(1-40) morphology.Peptides 06/2003; 24(5):679-85. · 2.43 Impact Factor -
Article: The effect of fibrillar A Beta 1-40 on membrane fluidity and permeability.
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ABSTRACT: The time course of A beta fibril formation was characterized using a variety of assays. The effect of A beta on the membrane fluidity and permeability was assessed by monitoring the anisotropy of the fluorescent probe DPH and TMA-DPH and measuring the release of vesicle-entrapped with three different molecular weight fluorescence probes (ANTS/DPX, Calcein, FD-4). The results show fibrils had formed after 4 days. Aggregated A beta may decrease the membrane fluidity and induce the leakage of ANTS and Calcein in a dose dependent manner. These effects may have some relation with A beta neurotoxicity.Protein and Peptide Letters 05/2002; 9(2):173-8. · 1.94 Impact Factor
Top co-authors
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Institutions
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2012
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Peking University Health Science Center
Beijing, Beijing Shi, China
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2002–2012
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Peking University
- School of Basic Medical Science
Beijing, Beijing Shi, China
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