Sequence and structural determinants of amyloid fibril formation

Amyloid fibril formation is a process that represents an essential feature of the chemistry of proteins and plays a central role in human pathology and the biology of living organisms. In this Account, we shall describe some of the recent results on the sequence and structural determinants of protein aggregation. We shall describe the factors that govern aggregation of unfolded peptides and proteins. We shall then try to summarize the factors that pertain to the aggregation of partially structured states and will show that even fully folded states of proteins have an ability to aggregate into at least early oligomers with no need to undergo substantial conformational changes.     

The role of nanoclay partitioning and fibril formation on dyeability of blend nanocomposite fibres

The aim of the present work was to study the effect of microstructure and microfibril formation on dyeability of polypropylene/poly(butylene terephthalate)/organoclay blend nanocomposite fibres. The blend nanocomposite samples with the same blend ratio but varying in organoclay content were prepared via melt compounding by using a co‐rotating twin screw extruder. The microfibrillar morphology and nanoclay partitioning were studied using scanning electron microscopy and transmission electron microscopy together with rheological results. The presence of nanoclay in the form of tactoids in the polypropylene matrix accelerated the dye sorption but much greater ultimate dye uptake could be achieved for the sample in which the major part of the platelets were preferentially located inside the poly(butylene terephthalate) fibrils. Although increasing the organoclay concentration increased the ultimate dye uptake, it limited the fibril formation at higher organoclay concentration. The utilisation of a compatibiliser was found to have an enhancing effect on ultimate dye uptake. This could be explained in terms of the interfacial role of the compatibiliser in improving microfibril formation as well as partitioning a fraction of nanoclay platelets inside the polypropylene matrix.     

A multimeric quinacrine conjugate as a potential inhibitor of Alzheimer's beta-amyloid fibril formation

Amyloid formation and accumulation of the amyloid beta-peptide (Abeta) in the brain is associated with Alzheimer's disease (AD) pathogenesis. Therefore, among the therapeutic approaches in development to fight the disease, the direct inhibition of the Abeta self-assembly process is currently widely investigated and is one of the most promising approaches. In this study we investigated the potential of a multimeric display of quinacrine derivatives, as compared to the monomer quinacrine, as a design principal for a novel class of inhibitors against Abeta fibril formation. The presented multimeric conjugate exhibits a cluster of four quinacrine derivatives on a rigid cyclopeptidic scaffold. Herein is reported the synthesis of the conjugate, together with the in vitro inhibitory evaluation of Abeta(1-40) fibrils using the thioflavin T fluorescence assay, and imaging with atomic force microscopy. Our data show that the multimeric compound inhibits Abeta(1-40) fibril formation with an IC(50) value of 20+/-10 microM, which contrasts with the nonactive monomeric analogue. This work suggests that assembling multiple copies of acridine moieties to a central scaffold, for multiple interactions, is a promising strategy for the engineering of inhibitors against Abeta fibril formation.     

Effect of layered silicates on fibril formation and properties of PCL/PLA microfibrillar composites

The study deals with improvement of poly(?‐caprolactone) (PCL) parameters by in situ forming of poly(lactic acid) (PLA) fibrils. This structure is achieved by preparation of the melt‐drawn microfibrillar composite (MFC) from the PCL/PLA 80/20 blend containing the organophilized montmorillonite (oMMT) added using various mixing protocols. Improved mechanical behavior corresponds to the micron‐sized fibrils formation and reinforcement of both polymer components by oMMT, and to increased crystalline phase content in the fibrillar PLA phase. Effective melt drawing is only possible after the rheological parameters of the polymer components have been modified by oMMT where the clay addition method and content are of primary importance. From the results obtained, it follows that the role of oMMT in MFC is quite complex, numerous clay‐induced effects may be contradictory and must be harmonized to achieve PCL‐based biodegradable MFCs with improved parameters. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43061.     

Craze initiation and growth in high-impact polystyrene

Quantitative transmission electron microscopy and optical microscopy is used to study craze initiation and growth in thin films of high-impact polystyrene (HIPS). Dilution of the HIPS with unmodified polystyrene reduces the craze–craze interactions, permitting equilibrium growth and craze micromechanics to be studied. It is found that the equilibrium craze length depends on the size of the nucleating rubber particle, but not the internal structure; no short crazes less than a particle diameter are observed. The long crazes can be adequately modelled by the Dugdale model for crazes grown from crack tips. The effects of particle size and particle internal occlusion structure on craze nucleation have been separated. Craze nucleation is only slightly enhanced at highly occluded particles relative to craze nucleation at solid rubber particles of the same size. There is a strong size effect, however, which is independent of particle internal structure. Crazes are rarely nucleated from particles smaller than ～1 μm in diameter, even though these make up about half the total number. These craze nucleation and growth effects may be understood in terms of two hypotheses for craze nucleation: (1) the initial elastic stress enhancement at the rubber particle must exceed the stress concentration at a static craze tip and (2) the region of this enhanced stress must extend at least three fibril spacings from the particle into the glassy matrix. Since the spatial extent of the stress enhancement scales with the particle diameter, the second hypothesis accounts in a natural way for the inability of small rubber particles to nucleate crazes.     

Yeast prion-protein, sup35, fibril formation proceeds by addition and substraction of oligomers

In analogy to human prions, a domain of the translation-termination protein in Saccharomyces cerevisiae, Sup35, can switch its conformation from a soluble functional state, [psi-], to a conformation, [PSI+], that facilitates aggregation and impairs its native function. Overexpression of the molecular chaperone Hsp104 abolishes the [PSI+] phenotype and restores the normal function of Sup35. We have recently shown that Hsp104 interacts preferably with low oligomeric species of a Sup35 derived peptide, Sup35[5-26]; however, due to possible exchange between different oligomeric states, it was not possible to obtain information on the distribution and stability of the oligomeric state. We show here, that low-molecular-weight oligomers (Sup35[5-26])n (n approximately = 4-6) are indeed important for the fibril formation and disassembly process. We find that Hsp104 is able to disaggregate Sup35[5-26] fibrils by substraction of hexameric to decameric Sup35[5-26] oligomers. This disaggregation effect does not require assistance from other chaperones and is independent of ATP at high Hsp104 concentrations. Furthermore, we demonstrate that critical oligomers have a preference for alpha-helical conformations. The conformational reorganization into beta-sheet structures seems to occur only upon incorporation of these oligomers into fibrillar structures. The results are demonstrated by using an equilibrium dialysis experiment that employed different molecular-weight cut-off membranes. A combination of thioflavin-T (ThT) fluorescence and UV measurements allowed the quantification of fibril formation and the amount of peptide diffusing out of the dialysis bag. CD and NMR spectroscopy data were combined to obtain structural information.     

Craze failure by midrib creep

It has been known for some time that crazes thicken during growth mainly by drawing in fresh material from the craze-bulk interface, keeping the average craze fibril draw ratio approximately constant. Since Creep effects contribute only negligibly to craze growth rates these effects have generally been considered unimportant regarding craze breakdown. However, it is also known that the first stage of fracture is failure of the craze midrib, which is a highly drawn, very thin region down the middle of a craze. Because of the very low thickness of the midrib it has little influence on craze behavior, and information on midrib behavior is difficult to obtain. It is the purpose of this paper to attempt to rationalize what information is available.     

Craze healing in polymer glasses

Craze healing was observed in many amorphous glassy polymers. A detailed study of the kinetics of craze healing in atactic polystyrene (M_w = 255,000) was conducted. The crazes were created in 0.08 mm films in air at room temperature, T_o, and constant stress, σ_o ? 2,300 psi, healed at temperature T_h for a time, T_h, at σ = 0, and recrazed at T_o and σ_o. Nucleation times, τ₁ and τ₂, and growth rates, L₁, and L₂, for the first and second loading, respectively, were measured as a function of t_h and T_h for individual crazes using dark field optical microscopy. Complete optical and mechanical healing was observed for T_h ? 70°C(T_g ? 100°C). At constant T_h, healing progressed in five stages with increasing th as follows; (i) no healing, τ₂ = 0, L₂ ? L₁; (ii) partial healing, τ₂ <τ₁, L₂ > L₁; (iii) similar growth, τ₂ = τ₁, L₂ = L₁; (iv) slower growth, τ₂ > τ₁, L₂ < L₁; (v) disappearance, τ₂ → ∞, L₂ → 0. A craze healing envelope of T_h vs T_h was obtained for the above stages. Craze healing occurred by line mode in which uniform healing occurred along the entire length of the craze.     

Theory of electrical breakdown during formation of barrier anodic films

The anodic formation of barrier oxide films on valve metals can be carried on till the electrode potential has attained the “breakdown voltage” (U_B, after which a sustained sparking appears. The systematization of the available data on this phenomenon revealed that U_B depends fundamentally on the nature of the anodized metal, as well as on the composition and resistivity of the electrolyte. Many other factors like the current density, the surface topography of the electrode, the history of the film formation, etc do not affect U_B noticeably. This phenomenology of the breakdowns, as well as their appearance, was explained by a breakdown model. According to this model, sparking is considered as an avalanching in the bulk of the anodic film, the initial electrons being injected into the film from the electrolyte. The peculiar features of the sparking were found to arise both from the specific injecting behaviour of the electrolyte and from the simultaneous oxide film formation.     

某有机玻璃零件银纹开裂分析及预防

针对某轨道交通有机玻璃零件的银纹开裂,介绍了其材料特性、零件结构及装配使用过程,分析了零件的尺寸、加工工艺、裂纹显微形貌。通过耐受试验及推理论证,发现银纹开裂的原因与加工应力大和外界有机溶剂有关。根据改进验证,改进加工工艺后的零件抗银纹开裂性显著增强,提出了进一步减少银纹开裂故障的建议措施。     

Craze kinetics for PMMA in liquids

Observations are reported on the growth of crazes in PMMA immersed in a range of alcohols, some less active crazing agents and some mixtures of methanol and inactive agents. When there is substantial plasticization of the craze, the growth is adequately described by the fluid flow model. Mixtures are also explicable in these terms since the active agent is preferentially absorbed. For lower degrees of plasticization, the craze growth is small and probably relaxation controlled.     

Craze plasticity and toughness of particulate block copolymer blends

Blends of KRO-1 Resin in high molecular weight polystyrene in which the K-Resin appears as dispersed spherical composite particles with the characteristic K-Resin morphology have been modified by incorporating into them additional polybutadiene of a molecular weight of 3 kg/mole (PB3K). It was found that small additions of PB3K into KRO-1 initiate first a morphological transformation resulting in particles with two coexisting morphologies of distorted rods and parallel lamellae. At a ratio of PB3K/KRO-1 of somewhat above 0.33 the transformation is complete and results in composite particles with a very regular concentric spherical shell morphology of PB and PS. The craze initiating effectiveness of composite particles peaks with this morphology, resulting in craze flow stresses as low as 8 MPa and strains to fracture in excess of 0.80 for a PB3K/KRO-1 ratio of 0.5. Larger volume concentrations of PB3K result in reprecipitation of free PB3K inside particles and this gives rise to a rapid degradation of toughness. The very effective craze initiating action of the spherical shell particles cannot be fully accounted for by the best techniques of numerical stress analysis of the elastic and thermal properties of the composite particles utilizing locally multiaxial craze initiation criteria that were developed for surface crazing in homo-PS. It is suspected that the craze initiation condition is locally relaxed around such composite particles by the presence of certain pre-existing ‘catalytic’ interface configurations that makes the nucleation of crazes from such particle interfaces more a heterogeneous nucleation phenomenon than a homogeneous nucleation phenomenon.     

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Craze dissemination during fatigue fracture in polystyrene

Results of studies on fatigue fracture in polystyrene are reported. Experiments were carried out on tension-tension single edge notched specimens, 0.25 mm thick. Macroscopic studies involved the propagation of the crack and its associated active zone (or the so-called process zone) evolution. Microscopic studies consisted of fracture surface examination and quantitative characterization of the crazing distribution along the trailing edge and within the active zone. The width and length of the active zone increased monotonically during the quasi-static phase of crack layer growth. The crack growth kinetics followed an S-shaped curve. Analysis of crazing distribution showed that; (i) the distribution of crazing along the trailing edge of the active zone is related by a scaling parameter, (ii) the average crazing density along the trailing edge as well as within the active zone is constant, (iii) the specific energy of crazing evaluated here compares well with previously reported data. The results of this work support the form of self similarity of damage evolution adopted by the crack layer model, and that the specific energy of damage is a material constant.     

Craze and creep resistance of high-impact polystyrene in alcohols

In the present state of development of the polymer industry, all of the lower cost, widely used, plastics exhibit some susceptibility to environmental stress crazing. Past developments have improved some polymers' resistance to this phenomenon (e.g., the addition of rubber to polystyrene) and this paper considers one such improved polymer, high-impact polystyrene, and examines its craze and creep resistance in the alcohols. This family of fluids does not affect the unstressed polymer but has a marked effect when the polymer is stressed. The results of creep tests at different stresses indicate the existence of a delay time after which the creep rate accelerates rapidly. The requirement of a definitive time under stpess before this acceleration occurs is supported by the results of cyclic stress tests. Plots of delay time against stress for the different alcohols show two distinct regions: (i) at high stresses, where the delay time increases from methanol to butanol and the mechanism would appear to be one of molecular volume controlling the mobility of the fluid to “penetrate” the polymer, and (ii) at low stresses, where the delay time decreases from methanol to butanol and the criterion would appear to be that of ability to “plasticize” the polymer as evidenced by the solubility parameters.     

Craze initiation in glassy polymers - Revisited

In spite of the continued interest in the yield, flow and fracture behavior of glassy homopolymers and the important role that crazing plays in their ultimate mechanical response, the basic understanding of the molecular level processes that govern craze initiation still remains murky. Here we revisit some early experiments of Argon and Hannoosh of the 1970s on craze initiation in homo polystyrene under combinations of both deviatoric shear stress and mean normal stress and also take note of more recent computer simulations of ultimate plastic flow and cavitation response of model glassy polymers. We then formulate a new craze initiation model and compare its predictions with the earlier experiments to find much better agreement over a wider range of applicability that sheds new light on this hitherto inadequately understood phenomenon.     

Craze shape and fracture in poly(methyl methacrylate)

The shape of the primary craze at the tip of a crack has been studied by optical microscopy for two grades of poly(methyl methacrylate). The craze shapes are compared with the predictions of the Dugdale model for the plastic zone at a crack tip, and used to obtain a quantitative estimate of the craze stress and the effective stress intensity factor. The values of the stress intensity factor are then compared with those obtained directly from fracture toughness measurements.