Morphology Of Aggregates Research Articles

Biospeckle laser as a tool to analyze erythrocyte aggregation

We analyze the erythrocyte aggregation by the biospeckle laser phenomenon and calculate characteristic parameters to develop non-invasive hemorheological techniques. Biospeckle is more complex than other light-based techniques, such as light transmission, providing information about the dynamics of the scatterers, their size, and morphology. Dextran 500 kDa combined with plasma and phosphate-buffered saline was used to induce controlled in vitro erythrocyte aggregation. Red blood cell aggregation was studied using an objective speckle setup in a microchip sample chamber. The speckle grain sizes were determined, and parameters to characterize the morphology of the erythrocyte aggregates were proposed. The inertia moment and the correlation coefficient were determined to assess the cells aggregation dynamics.

Impact of Hydrophobic/Hydrophilic Balance on Aggregation Pathways, Morphologies, and Excited-State Dynamics of Amphiphilic Diketopyrrolopyrrole Dyes in Aqueous Media.

We report the thermodynamic and kinetic aqueous self-assembly of a series of amide-functionalized dithienyldiketopyrrolopyrroles (TDPPs) that bear various hydrophilic oligoethylene glycol (OEG) and hydrophobic alkyl chains. Spectroscopic and microscopic studies showed that the TDPP-based amphiphiles with an octyl group form sheet-like aggregates with J-type exciton coupling. The effect of the alkyl chains on the aggregated structure and the internal molecular orientation was examined via computational studies combining MD simulations and TD-DFT calculations. Furthermore, solvent and thermal denaturation experiments provided a state diagram that indicates the formation of unexpected nanoparticles during the self-assembly into nanosheets when longer OEG side chains are introduced. A kinetic analysis revealed that the nanoparticles were obtained selectively as an on-pathway intermediate state toward the formation of thermodynamically controlled nanosheets. The metastable aggregates were used for seed-initiated supramolecular assembly, which allowed establishing control over the assembly kinetics and the aggregate size. The sheet-like aggregates prepared using the seeding method exhibited coherent vibration in the excited state, indicating a well-ordered orientation of the TDPP units. These results underline the significance of fine tuning of the hydrophobic/hydrophilic balance in the molecular design to kinetically control the assembly of amphiphilic π-conjugated molecules into two-dimensional nanostructures in aqueous media.

Drastically different restructuring of airborne and surface-anchored soot aggregates

Combustion soot particles are fractal aggregates of hydrophobic spherules. Mixing of soot particles with other chemicals during atmospheric processing may partially offset their hydrophobicity, promoting water uptake and structural compaction. We investigated morphological changes in fractal soot particles coated by sulfuric acid and then humidified, both in airborne and surface-bound states. Airborne soot was probed by tandem differential mobility analysis. Surface-bound soot was studied in a controlled microenvironment of a closed cell, using environmental transmission electron microscopy. After humidification, the airborne particles became fully compact, but the deposited particles showed only minor morphological changes despite significant water uptake. Although minor, those changes were detected during both water condensation and evaporation, indicating that condensation-evaporation cycles play an important role in atmospheric soot compaction. Lesser restructuring of deposited aggregates was caused by surface anchoring and coating loss, making anchoring an indispensable tool for preserving morphology of aggregates against changing experimental environment.

Mutant SOD1 aggregates formed in vitro and in cultured cells are polymorphic and differ from those arising in the CNS.

Mutations in the human Superoxide dismutase 1 (hSOD1) gene are well-established cause of the motor neuron disease ALS. Patients and transgenic (Tg) ALS model mice carrying mutant variants develop hSOD1 aggregates in the CNS. We have identified two hSOD1 aggregate strains, which both transmit spreading template-directed aggregation and premature fatal paralysis when inoculated into adult transgenic mice. This prion-like spread of aggregation could be a primary disease mechanism in SOD1-induced ALS. Human SOD1 aggregation has been studied extensively both in cultured cells and under various conditions in vitro. To determine how the structure of aggregates formed in these model systems related to disease-associated aggregates in the CNS, we used a binary epitope-mapping assay to examine aggregates of hSOD1 variants G93A, G85R, A4V, D90A, and G127X formed in vitro, in four different cell lines and in the CNS of Tg mice. We found considerable variability between replicate sets of in vitro-generated aggregates. In contrast, there was a high similarity between replicates of a given hSOD1 mutant in a given cell line, but pronounced variations between different hSOD1 mutants and different cell lines in both structures and amounts of aggregates formed. The aggregates formed in vitro or in cultured cells did not replicate the aggregate strains that arise in the CNS. Our findings suggest that the distinct aggregate morphologies in the CNS could result from a micro-environment with stringent quality control combined with second-order selection by spreading ability. Explorations of pathogenesis and development of therapeutics should be conducted in models that replicate aggregate structures forming in the CNS.

Large-Scale Production of Wholly Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors.

Combining the sustainable culture of billions of human cells and the bioprinting of wholly cellular bioinks offers a pathway toward organ-scale tissue engineering. Traditional 2D culture methods are not inherently scalable due to cost, space, and handling constraints. Here, the suspension culture of human induced pluripotent stem cell-derived aggregates (hAs) is optimized using an automated 250 mL stirred tank bioreactor system. Cell yield, aggregate morphology, and pluripotency marker expression are maintained over three serial passages in two distinct cell lines. Furthermore, it is demonstrated that the same optimized parameters can be scaled to an automated 1 L stirred tank bioreactor system. This 4-day culture results in a 16.6- to 20.4-fold expansion of cells, generating approximately 4 billion cells per vessel, while maintaining >94% expression of pluripotency markers. The pluripotent aggregates can be subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture-to-3D bioprinting pipeline that enables a sustainable approach to billion cell-scale organ engineering.

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry Approach to Correlate Local Structure and Aggregation in α-Synuclein.

In Parkinson's disease and other synucleinopathies, α-synuclein misfolds and aggregates. Its intrinsically disordered nature, however, causes it to adopt several meta-stable conformations stabilized by internal hydrogen bonding. Because they interconvert on short timescales, monomeric conformations of disordered proteins are difficult to characterize using common structural techniques. Few techniques can measure the conformations of monomeric α-synuclein, including millisecond hydrogen/deuterium-exchange mass spectrometry (HDX-MS). Here, we demonstrate a new approach correlating millisecond HDX-MS data with aggregation kinetics to determine the localized structural dynamics that underpin the self-assembly process in full-length wild-type monomeric α-synuclein. Our custom instrumentation and software enabled measurement of the amide hydrogen-exchange rates on the millisecond timescale for wild-type α-synuclein monomer up to residue resolution and under physiological conditions, mimicking those in the extracellular, intracellular, and lysosomal cellular compartments. We applied an empirical correction to normalize measured hydrogen-exchange rates and thus allow comparison between drastically different solution conditions. We characterized the aggregation kinetics and morphology of the resulting fibrils and correlate these with structural changes in the monomer. Applying a correlative approach to connect molecular conformation to aggregation in α-synuclein for the first time, we found that the central C-terminal residues of α-synuclein are driving its nucleation and thus its aggregation. We provide a new approach to link the local structural dynamics of intrinsically disordered proteins to functional attributes, which we evidence with new details on our current understanding of the relationship between the local chemical environment and conformational ensemble bias of monomeric α-synuclein.

Ganglioside GM3 stimulates lipid-protein co-assembly in α-synuclein amyloid formation

Parkinson's disease is characterized by the aggregation of the presynaptic protein α-synuclein (αSyn), and its co-assembly with lipids and other cellular matter in the brain. Here we investigated lipid-protein co-assembly in a system composed of αSyn and model membranes containing the glycolipid ganglioside GM3. We quantified the uptake of lipids into the co-assembled aggregates and investigated how lipid molecular dynamics is altered by being present in the co-assemblies using solution 1H- and solid-state 13C NMR spectroscopy. Aggregate morphology was studied using cryo-TEM. The overall lipid uptake in the co-assembled aggregates was found to increase with the molar ratio of GM3 in the vesicles. The lipids present in the co-assembled aggregates have reduced acyl chain and headgroup dynamics compared to the protein-free bilayer system. These findings may improve our understanding of how different types of lipids can influence the composition of αSyn aggregates, which may have consequences for amyloid formation in vivo.

Simulation of Micron and Submicron Particle Trapping by Single Droplets with Electrostatic Fields

Wet electrostatic precipitators have problems such as uneven water distribution and poor economy in applying ultra-clean particulate matter emissions from coal-fired boilers. Upgrading the droplets in wet dust removal to charged mobile collectors can effectively compensate for these shortcomings. In this paper, the effects of particle sphericity, particle size, and charge on the capture efficiency of a single droplet for capturing micron and submicron particles are qualitatively studied by simulating the process of particle capture by charged droplets in a turbulent flow field. The simulation results show that the trapping efficiency of charged droplets is positively correlated with the sphericity and the amount of charge. The particle size significantly impacts the capture efficiency, and the increase in size increases the capture efficiency, and the capture efficiency of 5.49 μm particles reaches 100%. The effect of particle movement speed on the capture efficiency needs to be considered in combination with particle size. For micron particles, the capture efficiency is close to 100% when the movement speed is 0.3 m/s and 0.5 m/s. For submicron particles, the aggregation morphology is lower at lower speeds. Simple non-spherical particles have greater capture efficiency.

Self-assembly of anionic surfactant and its effect on oil–water interface: Implications for enhanced oil recovery

Surfactant micellization is a self-assembly process governed by complex interplay of solvent-mediated interactions. However, quantitative modeling of micelle formation and its effect on oil–water interface are not yet completely understood. In this work, dissipative particle dynamics simulations were used to investigate the self-assembly behavior of anionic surfactants of alcohol alkoxy sulfate (AAS) and its structural influence on the interfacial properties of oil–water at the mesoscopic scale. Our results indicate that with the increase of surfactant concentration, the morphology of surfactant aggregates varied from spherical micelles to rod-shaped micelles, and finally formed worm-like micelles. The larger the number of propylene oxide (PO) groups, the easier the formation of large micelles and the more tightness of formed micelles. On the oil–water interface, the interfacial tension of solutions decreased with increasing surfactant concentration below the critical micelle concentration, whereas a positive correlation was found for the tightness of surfactant arrangement. When surfactants formed micelles, the overall coverage area of AAS decreased and a lower root mean square end distance of individual PO group directly affected interfacial properties of AAS. The obtained results could provide a solid theoretical basis for the rational design of efficient surfactants in oil recovery and soft matter applications.

Amyloid-like aggregation influenced by lead(II) and cadmium(II) ions in hen egg white ovalbumin

The aggregation of proteins into fibrillar, amyloid-like aggregates generally results in an improved, positive effect on various techno-functional properties within food products, such as gelation, emulsification, and foam stabilization. These highly stable structures, characterized by their repetitive, β-sheet rich motifs, may develop as the result of the thermal treatment of protein-rich food products. Heavy metal ions can influence amyloid-like aggregation of food proteins. Lead(II) and cadmium(II) represent some of the most abundant and common environmental water and food pollutants.In this work, the influence of heavy metal ions, lead and cadmium on amyloid-like aggregation of ovalbumin at high temperatures (90 °C) and under acidic conditions (pH 2.0) was investigated. Ovalbumin is used as a general model for how heavy metals can affect amyloid-like aggregation of a food protein. Structural changes were monitored via Thioflavin T and 8-Anilino-1-naphthalenesulfonic acid fluorescence, Fourier-Transform infrared spectroscopy, atomic force microscopy, dynamic light scattering, as well as computational analyses. The obtained results indicate that the added heavy metal ions bind to different sites within ovalbumin prior to thermal treatment. Lead binding sites are closer to the hydrophobic regions of an protein, while cadmium ion binding sites are more exposed. This specific binding of metal ions affects the morphologies of amyloid-like aggregates, resulting in lead-induced branching of amyloid-like fibrils, or cadmium-induced tangling of fibrils into dense amyloid clusters. This additive effect of heavy metal ions is most evident in ovalbumin samples which contain a mixture of both heavy metal ions.

Tuning the 3D microenvironment of reprogrammed tubule cells enhances biomimetic modeling of polycystic kidney disease

Renal tubular cells frequently lose differentiation markers and physiological properties when propagated in conventional cell culture conditions. Embedding cells in 3D microenvironments or controlling their 3D assembly by bioprinting can enhance their physiological properties, which is beneficial for modeling diseases in vitro.A potential cellular source for modeling renal tubular physiology and kidney diseases in vitro are directly reprogrammed induced renal tubular epithelial cells (iRECs). iRECs were cultured in various biomaterials and as bioprinted tubular structures. They showed high compatibility with the embedding substrates and dispensing methods. The morphology of multicellular aggregates was substantially influenced by the 3D microenvironment. Transcriptomic analyses revealed signatures of differentially expressed genes specific to each of the selected biomaterials. Using a new cellular model for autosomal-dominant polycystic kidney disease, Pkd1−/− iRECs showed disrupted morphology in bioprinted tubules and a marked upregulation of the Aldehyde dehydrogenase 1a1 (Aldh1a1). In conclusion, 3D microenvironments strongly influence the morphology and expression profiles of iRECs, help to unmask disease phenotypes, and can be adapted to experimental demands. Combining a direct reprogramming approach with appropriate biomaterials will facilitate construction of biomimetic kidney tubules and disease models at the microscale.

Explicit Polarization in Coarse-Grained Simulations of Ionomer Melts

The structure and morphology of ionic aggregates in ionomer melts significantly influence their ion transport properties. Understanding the underlying mechanisms and relevant time scales of ion transport can facilitate design of viable ionomer materials as single-ion conductors for energy applications. Previous studies have characterized the ionic aggregate structure, morphology, and dynamics using non-polarizable coarse-grained molecular dynamics (CGMD) simulations. In this work, we examine the role of polarization in ionomer melts by explicitly incorporating Drude oscillators in CGMD simulations. We systematically study the structure and dynamics of pendant ionomers, focusing on the comparison to non-polarizable systems. Polarization within the ion clusters leads to less overall ion structuring. On the aggregate scale, less ion structuring yields smaller ionic aggregates. The extent to which the clusters are smaller delicately depends on the strength of the electrostatic interactions (the dielectric constant). Under certain conditions, we find that the time scale for free counterion diffusion does not depend on the morphology, unlike that in a non-polarizable model.

Phase Behavior and Aggregate Transition Based on Co-assembly of Negatively Charged Carbon Dots and a pH-Responsive Tertiary Amine Cationic Surfactant.

We studied the co-assembly of an oppositely changed binary mixture of selenium-doped carbon quantum dots (Se-CQDs) and N,N-dimethyl octylamide-propyl tertiary amine (DOAPA) through turbidity, ζ potential measurement, and cryogenic transmission electron microscopy (cryo-TEM) with the aim of fabricating supramolecular assemblies with multiple dimensions and novel morphologies. The Se-CQD/DOAPA binary mixture exhibited abundant phase behavior, in which an isotropic phase (I1) was first observed, followed by turbidity (T), precipitation (P), and a second isotropic phase (I2), as the DOAPA concentration increased. Then we focused on investigating the morphologies of samples. In cryo-TEM observations, spherical aggregates were observed in all phase sequences, whereas the aggregates have different ζ potentials and sizes. In the I2 phase, interesting nanocapsule-like aggregates and spindle-like aggregates can be identified in addition to spherical aggregates. In combination with the rheological behaviors of the I2 phase solution and the detailed structure of the aggregates from enlarged cryo-TEM images, it is possible that the Se-CQDs and DOAPA co-assemble with novel network-like building blocks. The turbid solutions were found to be responsive to pH in phase P, and spherical aggregates were obtained at pH 6.5 but turned into vesicles when the pH reached 5.0. On the basis of these findings, CQDs and surfactants can be good structural building blocks for supramolecular structures, and the diverse morphologies of aggregates offer the prospect of multiple applications in the future.

Ozonation/UV irradiation of dispersed Ag/AgI nanoparticles in water resources: stability and aggregation.

Proliferation of nanoparticles (NPs) as aqueous pollutants is a matter of growing concern today. The aggregation kinetics of colloidal bare silver (Ag, 20.5nm) and silver iodide (AgI, 15.3nm) NPs were investigated during ozone/ultraviolet (O3/UV) oxidation. Dynamic light scattering was applied to monitor the aggregation of NPs, and the z-average of treated samples was considered aggregate diameter. The effect of temperature, pH, and initial concentration of NPs was investigated on the aggregation rate constant and stability ratio. At a short oxidation period of approximately 1min, the lower stability ratio was achieved for Ag NPs (< 50) than AgI NPs (> 100). Under acidic conditions, the negative surface charge of both NPs was neutralized that resulted in faster aggregation. In contrast, the impact of temperature and initial concentration of NPs on the aggregation rate was different for both NPs, which was due to the type of O3/UV interaction with the surface of NPs and the thickness of the electrical double layer surrounding the NPs. The aggregation behavior of Ag NPs obeyed diffusion-limited regime, while an intermediate regime between diffusion- and reaction-limited was observed for AgI NP aggregation. The resulting aggregate morphologies showed that the clusters were ramified for Ag and compressed for AgI NPs. Applying the O3/UV oxidation process for water treatment purposes leads to a significant reduction in aggregation time for inherently unstable Ag and stable AgI toxic NPs from several hours or days to several minutes.

Identifying C. elegans lifespan mutants by screening for early-onset protein aggregation

Genetic screens are widely used to identify genes that control specific biological functions. In Caenorhabditis elegans, forward genetic screens rely on the isolation of reproductively active mutants that can self-propagate clonal populations. Screens that target post-reproductive phenotypes, such as lifespan, are thus challenging. We combine microfluidic technologies and image processing to perform high-throughput automated screening for short-lived mutants using protein aggregation as a marker for aging. We take advantage of microfluidics for maintaining a reproductively active adult mutagenized population and for performing serial high-throughput analysis and sorting of animals with increased protein aggregation, using fluorescently-labeled PAB-1 as a readout. We demonstrate that lifespan mutants can be identified by screening for accelerated protein aggregation through quantitative analysis of fluorescently labeled aggregates while avoiding conditional sterilization or manual separation of parental and progeny populations. We also show that aged wildtypes and premature aggregation mutants differ in aggregate morphology, suggesting aggregate growth is time-dependent.

Influence of fine aggregate's morphology on mortars' rheology

This study investigates the influence of fine aggregate's morphology on mortars' rheology. To begin with, the authors gathered a sample of aggregates with different morphology and similar size and gradation, as these are very important physical properties affecting rheology. Then, the authors quantitatively described the fine aggregate's morphology at three different scales (macroscopic, mesoscopic, and microscopic), in terms of shape, angularity, and surface texture. To characterize quantitatively those morphology properties, the parameters sphericity, roundness and fractal dimension, respectively, were selected. The results show that the morphology of fine aggregates is properly characterized by these three parameters as the characterisation techniques returned different sphericity, roundness, and fractal dimension for the aggregates in the sample and the parameters presented different trends (i.e. the parameters are independent). Moreover, the rheological behaviour of mortars prepared with the sampled aggregates show large differences, indicating that the fine aggregate's morphology has a noticeable impact on mortars' rheology. Finally, based on the discussion and analysis of the experimental results, the influence of fine aggregate's morphology can be attributed to the coupled effect of the packing density, specific surface area, and equivalent diameter of fine aggregate, and this coupled effect can be visualized using a parameter D/PFT (ratio of equivalent diameter, D, to paste film thickness, PFT). Mortar prepared with fine aggregate with a poorer morphology has a larger D/PFT value, corresponding to higher relative yield stress and relative plastic viscosity. In addition, combining previous results of the authors, it is argued that D/PFT can be used as a universal parameter to assess the rheological properties of mortars.

Review of Visualization Technique and Its Application of Road Aggregates Based on Morphological Features

The sustainable performance of asphalt pavement depends on the quality and mix design of road aggregates. Identifying aggregate morphology and size is a prerequisite step for material design and numerical modeling of asphalt mixtures. The paper aims to review the morphometric measurement, characteristic parameters and visualization technique of road aggregates. Types, calculation methods and advantages of aggregate morphological characteristics are highlighted. The applications of aggregate morphological features on the volumetric design, compaction processes, mechanical properties and size effect of asphalt mixtures are summarized. Although digital image processing technology has been studied for years, aggregates in the complex accumulation are still difficult to measure accurately. In the current research, the morphological parameters of aggregates remain diverse without a standard protocol. Compared to theoretical models, numerical models have more difficulties establishing irregular morphology features in the simulated specimens but provide a volume parameter closer to the real value. The future investigation of road performance under dynamic loading should account for the microscopic evolution of shape, orientation and distribution of aggregates over time.

Effects of coarse aggregate morphology on concrete mechanical properties

The morphology of coarse aggregate can significantly affect the mechanical performance of concrete. In this study, the correlation between the compressive properties of concrete and the coarse aggregate morphology was systematically explored. Three kinds of aggregates with significant morphology differences were selected: Spherical Aggregates, Flaky Aggregates, and Elongated Aggregates. Three-dimensional morphological information was obtained by 3D Structured-Light Scanner, and quantitative statistical analyses were conducted to assess the distribution of morphological characteristics for these three-types aggregates. It is found that the three-type aggregates with the same mesh size can be properly discriminated through the axis length, flatness, elongation, the product of flatness and elongation, and sphericality. The simplex-centroid design was used to build the correlation between aggregate morphology and the compressive strengths of concrete with different water-cement ratios. The concrete with 100% spherical aggregates owns the highest compressive strength, which is higher than that of concrete mixed with other two aggregates by 9.4%–36.2% and 5.2%–28.8% at the curing of 3-day and 28-day, respectively. When the ratio of spherical aggregates reaches above 50%, the strength loss caused by the elongated aggregates and flaky aggregates content is not obvious. Further, the failure mechanism of concrete with 100% spherical aggregates, 100% flaky aggregates, and 100% elongated aggregates under cyclic loadings were investigated by X-ray computed tomography scanning. It is found that the cracks inside spherical aggregates concrete mainly initiate from the edges and the core section remains almost intact before the destruction by a major oblique crack. Meanwhile, the high residual strain after cyclic loadings can originate from the generated vertical cracks under compression. The research findings in this study can serve as a solid base for the designing of concrete structures.

Construction of Active Protein Materials: Manipulation on Morphology of Salmon Calcitonin Assemblies with Enhanced Bone Regeneration Effect.

The effect of protein drugs is always limited by their relatively low stability and fast degradation property; thus, various elegant efforts have been made to improve the bioactivity and biocompatibility of the protein drugs. Here, an alternative way is proposed to solve this problem. By simply adding a limited amount of small-molecular regulator, which tunes the subtle balance of protein-protein interactions (PPIs) and disulfide bond formation, the self-assembly property of the protein drug can be regulated, forming an "active protein material" itself. This means that, the resulting biomaterial is dominated by the protein drug and water, with significantly enhanced bone regeneration effect compared to the virgin protein in vitro and in vivo, through multivalent effect between the protein and receptor and the retarded degradation of the assembled proteins. In this active protein material, the protein drug is not only the active drug, but also the drug carrier, which greatly increases the drug-loading efficiency of the biomaterial, indicating the advantages of the easy preparation, high efficiency, and low cost of the active protein material with a bright future in biomedical applications.

Meso-scale computational modeling of the fracture of concrete with complex shaped aggregates under the self-restraint stress

Modelling irregularly shaped aggregates in concrete uses advanced algorithms to describe complex geometric profile of, e.g, crushed gravels. Consequently, discretization of the complex geometry and computational convergence of the resulting mesh scheme are the bottlenecks that prevent wider application of mesoscopic fracture simulation of concrete with more realistic aggregates. In this paper, a novel modelling framework with simple pre-processing and good computational convergence is proposed based on the diffuse meshing technique and the coupled elasto-viscoplastic damage model. The proposed model discretizes concrete using only regular elements that may have different material components such as aggregates, mortar matrix and aggregate/matrix interface. The accuracy of the proposed model is validated by comparing with the full three-phase model that meshes aggregate, mortar and their interfaces separately. The proposed model is applied then to investigate the failure mechanism of concrete under uniaxial compression and tension. Furthermore, the effect of using simplified aggregate meso-structure is studied by comparing the results of using the complex shaped aggregate models and the spherical shaped aggregate model. The results show that the morphology of aggregate has a no-negligible influence on post-peak mechanical behavior, the orientation of aggregate affects crack initiation and propagation, and self-restraint stresses reduce the strength of concrete.