261 research outputs found
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Amyloid formation: interface influence
The causes of pathological conditions
such as Alzheimer’s and Parkinson’s
diseases are becoming better
understood. Proteins that misfold from
their native structure to form aggregates
of β-sheet fibrils — termed amyloid — are
known1,2 to be implicated in these ‘amyloid
diseases’. Understanding the early steps
of fibril formation is critical, and the
conditions, mechanism and kinetics of
protein and peptide aggregation are being
widely investigated through a variety of
in vitro studies.
Kinetic aspects of the dispersion of the
protein or peptide in solution are thought
to influence the fibrillization process by
mass-transfer effects. In addition, mixing also
leads to shear forces, which can influence
fibril growth by perturbing the equilibrium
between the isolated and aggregated proteins,
causing existing fibrils to fragment and create
new nuclei3. Writing in the Journal of the
American Chemical Society, David Talaga
and co-workers have now highlighted4 an
additional factor that can influence the
fibrillization of amyloid-forming proteins —
the presence of hydrophobic interfaces
Nanoparticle Network Formation in Nanostructured and Disordered Block Copolymer Matrices
Incorporation of nanoparticles composed of surface-functionalized fumed silica (FS) or native colloidal silica (CS) into a nanostructured block copolymer yields hybrid nanocomposites whose mechanical properties can be tuned by nanoparticle concentration and surface chemistry. In this work, dynamic rheology is used to probe the frequency and thermal responses of nanocomposites composed of a symmetric poly(styrene-b-methyl methacrylate) (SM) diblock copolymer and varying in nanoparticle concentration and surface functionality. At sufficiently high loading levels, FS nanoparticle aggregates establish a load-bearing colloidal network within the copolymer matrix. Transmission electron microscopy images reveal the morphological characteristics of the nanocomposites under these conditions
Nanomaterials: Strenght in numbers
Self-assembly of proteins commonly associated with neurodegenerative diseases can be exploited to make well-ordered and strong functional macroscopic materials
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Self-assembly and anti-amyloid cytotoxicity activity of amyloid beta peptide derivatives
The self-assembly of two derivatives of KLVFF, a fragment Abeta(16-20) of the amyloid beta (Abeta) peptide, is investigated and recovery of viability of neuroblastoma cells exposed to Abeta is observed at sub-stoichiometric peptide concentrations. Fluorescence assays show that NH2-KLVFF-CONH2 undergoes hydrophobic collapse and amyloid formation at the same critical aggregation concentration (cac). In contrast, NH2-K(Boc)LVFF-CONH2 undergoes hydrophobic collapse at a low concentration, followed by amyloid formation at a higher cac. These findings are supported by the beta-sheet features observed by FTIR. Electrospray ionization mass spectrometry indicates that NH2-K(Boc)LVFF-CONH2 forms a significant population of oligomeric species above the cac. Cryo-TEM, used together with SAXS to determine fibril dimensions, shows that the length and degree of twisting of peptide fibrils seem to be influenced by the net peptide charge. Grazing incidence X-ray scattering from thin peptide films shows features of beta-sheet ordering for both peptides, along with evidence for lamellar ordering of NH2-KLVFF-CONH2. This work provides a comprehensive picture of the aggregation properties of these two KLVFF derivatives and show their utility, in unaggregated form, in restoring the viability of neuroblastoma cells against Abeta-induced toxicity
Fabrication of Highly Ordered Polymeric Nanodot and Nanowire Arrays Templated by Supramolecular Assembly Block Copolymer Nanoporous Thin Films
Realizing the vast technological potential of patternable block copolymers requires both the precise controlling of the orientation and long-range ordering, which is still a challenging topic so far. Recently, we have demonstrated that ordered nanoporous thin film can be fabricated from a simple supramolecular assembly approach. Here we will extend this approach and provide a general route to fabricate large areas of highly ordered polymeric nanodot and nanowire arrays. We revealed that under a mixture solvent annealing atmosphere, a near-defect-free nanoporous thin film over large areas can be achieved. Under the direction of interpolymer hydrogen bonding and capillary action of nanopores, this ordered porous nanotemplate can be properly filled with phenolic resin precursor, followed by curation and pyrolysis at middle temperature to remove the nanotemplate, a perfect ordered polymer nanodot arrays replication was obtained. The orientation of the supramolecular assembly thin films can be readily re-aligned parallel to the substrate upon exposure to chloroform vapor, so this facile nanotemplate replica method can be further extend to generate large areas of polymeric nanowire arrays. Thus, we achieved a successful sub-30 nm patterns nanotemplates transfer methodology for fabricating polymeric nanopattern arrays with highly ordered structure and tunable morphologies
Conjugation with L, L-diphenylalanine Self-Assemblies Enhances In Vitro Antitumor Activity of Phthalocyanine Photosensitizer
We present the synthesis and characterization of new peptide conjugates obtained by hierarchical co-assembly of L,L-diphenylalanine (FF) and zinc phthalocyanine complexes (ZnPc) in water. Self-assembly capabilities under defined conditions were investigated by scanning electron microscopy, and photophysical properties were evaluated using UV-Vis and fluorescence spectroscopy. AFM observations demonstrated that these ZnPcs form different highly ordered arrays on the crystalline faces of the FF microplates and that surface roughness significantly changes with the presence of differently substituted phthalocyanine units. XRD assays showed that the overall molecular packing of the conjugates is organized according to a hexagonal symmetry, with ZnPcs hosted in the interstices of the peptide phase. In vitro photodynamic studies were conducted on human breast cancer MCF-7 cells to investigate both cellular uptake and cytotoxicity. It was shown that FF self-assemblies are not toxicity and enhance accumulation of ZnPc in MCF-7 cells, improving apoptotic cell death upon irradiation. Our findings demonstrate enhancement of ZnPc antitumor efficiency by FF conjugates and a proof-of-concept for new photosensitizer carriers based on peptide conjugates
Synthesis and characterization of polystyrene-blockpoly(vinylbenzoic acid): a promising compound for manipulating photoresponsive properties at the nanoscale
"Published online: 27 January 2015"Using reversible addition-fragmentation chain
transfer (RAFT) polymerization, the effect of PSt macroRAFT
and 4VBA ratio on the synthesis of a carboxylic
acid functional block copolymer (PSt-b-P4VBA) was
studied. PSt macroRAFT polymer was initially prepared
followed by the insertion of 4-vinylbenzoic acid (4VBA)
monomer. The chemical structure of the diblock copolymer
was confirmed by NMR and FTIR. The effect of PSt
macroRAFT and 4VBA ratio on copolymerization yield
and on molecular weight distribution was assessed by gel
permeation chromatography. The rate of polymerization
did not change as the 4VBA/PSt macroRAFT ratio
increased, indicating an ideal amount of 4VBA insertion.
An optimal ratio of [PSt macroRAFT]:[AIBN]:[4VBA]
was 1.2:1:180. DSC and XRD confirmed the amorphous
structure of homo and copolymer. Thermal stability was
higher for PSt-b-P4VBA forming activated porous carbon
char by dehydration, carbonization and oxidation. SEM
and STEM observations showed a morphological evolution
between PSt macroRAFT and the correspondent
copolymer.The authors acknowledge the n-STeP-Nanostructured systems for Tailored Performance, with reference NORTE-07-0124-FEDER-000039, supported by the Programa Operacional Regional do Norte (ON.2), PEst-C/CTM/LA0025/2013 (Strategic Project-LA 25-2013-2014)
Non-Conjugated Small Molecule FRET for Differentiating Monomers from Higher Molecular Weight Amyloid Beta Species
Background:
Systematic differentiation of amyloid (Aβ) species could be important for diagnosis of Alzheimer's disease (AD). In spite of significant progress, controversies remain regarding which species are the primary contributors to the AD pathology, and which species could be used as the best biomarkers for its diagnosis. These controversies are partially caused by the lack of reliable methods to differentiate the complicated subtypes of Aβ species. Particularly, differentiation of Aβ monomers from toxic higher molecular weight species (HrMW) would be beneficial for drug screening, diagnosis, and molecular mechanism studies. However, fast and cheap methods for these specific aims are still lacking. Principal Findings:
We demonstrated the feasibility of a non-conjugated FRET (Förster resonance energy transfer) technique that utilized amyloid beta (Aβ) species as intrinsic platforms for the FRET pair assembly. Mixing two structurally similar curcumin derivatives that served as the small molecule FRET pair with Aβ40 aggregates resulted in a FRET signal, while no signal was detected when using Aβ40 monomer solution. Lastly, this FRET technique enabled us to quantify the concentrations of Aβ monomers and high molecular weight species in solution. Significance:
We believe that this FRET technique could potentially be used as a tool for screening for inhibitors of Aβ aggregation. We also suggest that this concept could be generalized to other misfolded proteins/peptides implicated in various pathologies including amyloid in diabetes, prion in bovine spongiform encephalopathy, tau protein in AD, and α-synuclein in Parkinson disease.National Institute on Aging (K25AG036760
Reactivity of Metal-Free and Metal-Associated Amyloid-?? with Glycosylated Polyphenols and Their Esterified Derivatives
Both amyloid-?? (A??) and transition metal ions are shown to be involved in the pathogenesis of Alzheimer???s disease (AD), though the importance of their interactions remains unclear. Multifunctional molecules, which can target metal-free and metal-bound A?? and modulate their reactivity (e.g., A?? aggregation), have been developed as chemical tools to investigate their function in AD pathology; however, these compounds generally lack specificity or have undesirable chemical and biological properties, reducing their functionality. We have evaluated whether multiple polyphenolic glycosides and their esterified derivatives can serve as specific, multifunctional probes to better understand AD. The ability of these compounds to interact with metal ions and metal-free/-associated A??, and further control both metal-free and metal-induced A?? aggregation was investigated through gel electrophoresis with Western blotting, transmission electron microscopy, UV-Vis spectroscopy, fluorescence spectroscopy, and NMR spectroscopy. We also examined the cytotoxicity of the compounds and their ability to mitigate the toxicity induced by both metal-free and metal-bound A??. Of the polyphenols investigated, the natural product (Verbascoside) and its esterified derivative (VPP) regulate the aggregation and cytotoxicity of metal-free and/or metal-associated A?? to different extents. Our studies indicate Verbascoside represents a promising structure for further multifunctional tool development against both metal-free A?? and metal-A??.open0
Nanospiral Formation by Droplet Drying: One Molecule at a Time
We have created nanospirals by self-assembly during droplet evaporation. The nanospirals, 60–70 nm in diameter, formed when solvent mixtures of methanol and m-cresol were used. In contrast, spin coating using only methanol as the solvent produced epitaxial films of stripe nanopatterns and using only m-cresol disordered structure. Due to the disparity in vapor pressure between the two solvents, droplets of m-cresol solution remaining on the substrate serve as templates for the self-assembly of carboxylic acid molecules, which in turn allows the visualization of solution droplet evaporation one molecule at a time
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