Cu(II) ions are implicated in the pathogenesis of Alzheimer disease by influencing the aggregation of the amyloid- (A)peptide. Elucidating the underlying Cu(II)-induced A aggregation is paramount for understanding the role of Cu(II) in the pathology of Alzheimer disease. The aim of this study was to characterize the qualitative and quantitative influence of Cu(II) on the extracellular aggregation mechanism and aggregate morphology of A 1-40 using spectroscopic, microelectrophoretic, mass spectrometric, and ultrastructural techniques. We found that the Cu(II):A ratio in solution has a major influence on (i) the aggregation kinetics/mechanism of A, because three different kinetic scenarios were observed depending on the Cu(II):A ratio, (ii) the metal:peptide stoichiometry in the aggregates, which increased to 1.4 at supra-equimolar Cu(II):A ratio; and (iii) the morphology of the aggregates, which shifted from fibrillar to non-fibrillar at increasing Cu(II):A ratios. We observed dynamic morphological changes of the aggregates, and that the formation of spherical aggregates appeared to be a common morphological end point independent on the Cu(II) concentration. Experiments with A 1-42 were compatible with the conclusions for A 1-40 even though the low solubility of A 1-42 precluded examination under the same conditions as for the A 1-40 . Experiments with A 1-16 and A 1-28 showed that other parts than the Cu(II)-binding His residues were important for Cu(II)-induced A aggregation. Based on this study we propose three mechanistic models for the Cu(II)-induced aggregation of A 1-40 depending on the Cu(II):A ratio, and identify key reaction steps that may be feasible targets for preventing Cu(II)-associated aggregation or toxicity in Alzheimer disease.Extracellular cerebral plaques composed mainly of amyloid -peptide (A) 1-40 and 1-42 fibrils are a histopathological hallmark of Alzheimer disease (AD) 3 (1, 2). These plaques contain elevated levels of metals, in particular zinc and copper (3). Also, it has been shown that these metal ions can promote the aggregation of A in vitro (4, 5). This implies a key role of the metal ions in the A-mediated pathology of AD (6), although the subject is still under much debate (7,8), and a role of amyloid-independent pathways in AD neurodegeneration have recently been reviewed (9).Specifically regarding the role of metal ions in the amyloidmediated pathology of AD, it is believed that Zn(II) acts as a neuroprotector (10, 11), whereas Cu(II) is considered to mediate neurotoxicity (12)(13)(14). The latter effect is thought to occur through early stage soluble A and A-Cu oligomeric intermediates (15-18) that may be involved in the formation of reactive oxygen species (6). It was discovered that Cu(II) may be released postsynaptically at glutamatergic synapses in hippocampus (19,20), the site for initial A deposition in AD. This provides an explanation for how Cu(II) can interact with A. Seemingly in contrast to the support for the neurotoxic effects of Cu(II),...
We have explored the effects of solvent, adsorber concentration, and environment on the formation of high-coverage monolayers of alkylsiloxanes on silicon oxide surfaces from alkylsiloxane solutions. Specifically, we have varied the solvent polarity and the concentration of octadecyltrichlorosilane (OTS) used for the deposition process. We found that for a wide range of concentrations (25 µM to 2.5 mM) and normal laboratory air humidity (RH 45-85%) OTS dissolved in heptane causes the formation of a full-coverage self-assembled monolayer on hydrophilic silicon oxide. The resulting self-assembled layers were studied by atomic force microscopy, ellipsometry, and X-ray reflectometry. Deposition of OTS from dodecane solutions resulted in multilayered films. In contrast, the use of heptane as solvent (in which the solubility of water is at intermediate level between toluene and dodecane) caused the formation of high-quality monolayers. We found consistent and reproducible results for the effect of solvents (dodecane and heptane) and conditions on the formation of OTS layers on Si/SiO2 surfaces. The substrates, which are covered by a full monolayer, function as well-defined ultraflat hydrophobic surfaces for other experiments.
The mechanism by which nanoparticles suspended in liquids self-organize on substrates to ring patterns has attracted much attention, because of a large body of possible practicable applications. Recent work demonstrated that, for example, gravity affects ring geometry, showing that the mechanism of ring formation is indeed not fully understood. Current models suppose that the pinning of the contact line between drops and substrates is a prerequisite for ring formation and that the process is induced either by surface irregularities of the substrate itself, or by self-pinning, triggered by the attachment of suspended material to the substrate. The latter mode was illustrated for drops of aqueous suspensions, evaporating on atomically flat hydrophilic substrates, e.g., freshly cleaved mica. Conversely, the crucial role of pinning on ring formation was derived from the observation that no rings were formed on smooth Teflon. Here we provide the first experimental evidence of the formation of rings on supersmooth hydrophobic surfaces lacking the known conditions required for particle immobilization. Results are suitable to extend existing models and are expected to be instrumental in the predictable design of cell-integrative crystalline ring patterns on biomaterial surfaces and the production of symmetrical ring patterns in proteomics, where the rings are particularly useful to study interaction scenarios between competing proteins.
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