Templating S100A9 amyloids on Aβ fibrillar surfaces revealed by charge detection mass spectrometry,microscopy, kinetic and microfluidic analyses

The mechanism of amyloid co-aggregation and its nucleation process are not fully understood in spite of extensive studies. Deciphering the interactions between proinflammatory S100A9 protein and Aβ₄₂ peptide in Alzheimer''s disease is fundamental since inflammation plays a central role in the disease onset. Here we use innovative charge detection mass spectrometry (CDMS) together with biophysical techniques to provide mechanistic insight into the co-aggregation process and differentiate amyloid complexes at a single particle level. Combination of mass and charge distributions of amyloids together with reconstruction of the differences between them and detailed microscopy reveals that co-aggregation involves templating of S100A9 fibrils on the surface of Aβ₄₂ amyloids. Kinetic analysis further corroborates that the surfaces available for the Aβ₄₂ secondary nucleation are diminished due to the coating by S100A9 amyloids, while the binding of S100A9 to Aβ₄₂ fibrils is validated by a microfluidic assay. We demonstrate that synergy between CDMS, microscopy, kinetic and microfluidic analyses opens new directions in interdisciplinary research.

Templating mechanism of S100A9 amyloids on Aβ fibrillar surfaces during amyloid co-aggregation process was revealed by synergy of biophysical methods including charge detection mass spectrometry, microscopy, kinetic and microfluidic analyses.     

The anomalous spectral dependence of polarization in comets

We have found an anomalous (negative) spectral dependence of polarization for split comet 73P/Schwassmann–Wachmann 3, i.e. polarization degree in the I filter is systematically less (4%) than that in the R filter for both B and C subnuclei of the comet. Earlier we revealed a similar effect for comets 21P/Giacobini–Zinner, C/1999 S4 (LINEAR), and 9P/Tempel 1. Together with comet C/1989 X1 (Austin), for which the similar spectral dependence of polarization was also observed, these comets form a group characterized by some peculiar properties of their dust. Since atypical organic composition is a characteristic feature for all these comets, the anomalous spectral dependence of polarization may indicate specifics of origin of these comets. Really, most of these comets (but not all) originated from the Kuiper Belt. Also, most (but not all) of these comets belong to the group of comets depleted in carbon species in the gas phase, which is typical for comets formed in the giant-planet area of the solar system. On the other hand, all of the comets with negative spectral gradient of polarization have the dust dominated by large particles and most of them belong to the Jupiter family. This may indicate that anomalous spectral dependence of their polarization is a result of their evolution. To identify the reason of anomalous polarization, systematic spectropolarimetric observations of Jupiter-family comets are necessary.     

A New Cu, Al Fluoride Disilicate CuAl2F2(Si2O7) and its Relations to Topaz

CuAl₂F₂(Si₂O₇) has been prepared by hydrothermal synthesis and its crystal structure was determined by single crystal X‐ray diffraction: space group Pnma, a = 8.8697(9), b = 14.084(2), c = 4.7553(5) Å, wR₂ = 0.056, R = 0.022. Cu²⁺ shows elongated square pyramidal coordination. Edge‐ and corner‐sharing [AlO₄F₂] octahedra with fluorine atoms in cis position form layers parallel to the ac plane. Along b these layers are linked by Si₂O₇ groups to form a three‐dimensional framework [Al₂F₂(Si₂O₇]^2–. In addition, the [CuO₅] pyramides connect two Al octahedra of neighbouring layers. The crystal structure is discussed as a derivative from topaz structure. The modular (or polysomatic) approach is used for this purpose, and for modelling hypothetical related compounds.     

Scattering by inhomogeneous particles: microwave analog experiments and comparison to effective medium theories

It is common practice to use effective medium theories (EMT) to estimate average, “effective” optical constants of inhomogeneous materials. A variety of EMTs were developed for different internal structures of the medium and for a variety of shapes, size distributions and physical properties of the inhomogeneities. The most popular EMTs (Maxwell Garnett, Bruggeman, Looyenga, etc.) consider inhomogeneities that are much smaller than the wavelength. The so-called extended EMTs were developed to find effective optical constants in the case of inhomogeneities comparable and slightly larger than the wavelength. This paper compares angular distribution and wavelength dependence of intensity and polarization of scattered light obtained from calculations using the most popular EMTs and extended EMTs with the results of microwave analog measurements at the microwave facilities of the University of Florida. We simulated the light scattering by organic grains with silicate inclusions of size parameter x=0.075 (≈0.01 μm), 0.60 (≈0.1 μm), and 1.24 (≈0.2 μm). The conclusion is that for inclusions of a small size and for a small volume fraction of them in the mixture all EMTs yield similar results and show reasonable agreement with experimental results. The accuracy is better for the angular dependencies of the intensity and of the polarization of the scattered light than for their wavelength dependencies. For inhomogeneities comparable and larger than the wavelength extended EMTs work better but for smaller inclusions non-extended EMTs show more accurate results. Large volume fractions of the inclusions in the mixture (>10%) essentially reduce the accuracy of the results obtained with EMTs. Based on our study we do not recommend to use EMTs in the back-scattering domain and at the scattering angles 30°<θ<70°.     

Modeling variations in near-infrared spectra caused by the coherent backscattering effect

We study a new optical effect, a spectral manifestation of coherent backscattering, which reveals itself as systematic variations in the depth of absorption bands with changing phase angle. We used Cassini VIMS near-infrared spectra of Saturn's icy satellite Rhea in order to identify and characterize the spectral change with phase angle, focusing on the change in the depth of water-ice absorption bands. To model realistic characteristics of the surfaces of icy satellites, which are most likely covered by micron-sized densely packed particles, we perform simulations using a theoretical approach based on direct computer solutions of the macroscopic Maxwell equations. Our results show that this approach can reproduce the observed phase-angle variations in the depth of the absorption bands. The modeled changes in the absorption bands are strongly affected by physical properties of the regolith, especially by the size and packing density of the ice particles. Thus, the phase-angle spectral variations demonstrate a promising remote-sensing capability for studying properties of the surfaces of icy bodies and other objects that exhibit a strong coherent backscattering effect.     

T-matrix approach to calculating circular polarization of aggregates made of optically active materials

Optical activity is a typical property of the biological materials where left-handed amino-acids and right-handed carbohydrates dominate (so called homochirality). Observationally, optically active materials reveal themselves through the circular polarization in the light they scatter. Thus, circular polarization produced by the optically active particles can serve as a biomarker. It is known that biological (e.g. colonies of bacteria) and pre-biological (e.g. dust in comets) particles often have a complex structure that can be modeled presenting them as aggregates of small monomers. This motivated the development of the T-matrix code presented in this paper, which enables calculation of the scattering matrix - including circular polarization - of the light scattered by aggregated optically active particles. The code can be used for modeling the light scattering by biological objects (e.g. colonies of bacteria, blood cells) and for interpretation of the circular polarization produced by the cosmic dust that contains (pre)biological organic, e.g. comet dust or planetary aerosols.     

Adsorption and reduction of glutathione disulfide on α-Al2O3 nanoparticles: experiments and modeling

Glutathione disulfide (GSSG; γ-GluCysGly disulfide) was used as a physiologically relevant model molecule to investigate the fundamental adsorption mechanisms of polypeptides onto α-alumina nanoparticles. Its adsorption/desorption behavior was studied by enzymatic quantification of the bound GSSG combined with zeta potential measurements of the particles. The adsorption of GSSG to alumina nanoparticles was rapid, was prevented by alkaline pH, was reversed by increasing ionic strength, and followed a nearly ideal Langmuir isotherm with a standard Gibbs adsorption energy of -34.7 kJ/mol. Molecular dynamics simulations suggest that only one of the two glutathionyl moieties contained in GSSG binds stably to the nanoparticle surface. This was confirmed experimentally by the release of GSH from the bound GSSG upon reducing its disulfide bond with dithiothreitol. Our data indicate that electrostatic interactions via the carboxylate groups of one of the two glutathionyl moieties of GSSG are predominantly responsible for the binding of GSSG to the alumina surface. The results and conclusions presented here can provide a base for further experimental and modeling studies on the interactions of biomolecules with ceramic materials.