Promoting Cluster Formation Research Articles

Dynamical clustering and wetting phenomena in inertial active matter

Dynamical clustering is a key feature of active matter systems composed of self-propelled agents that convert environmental energy into mechanical motion. At the micron scale, where overdamped dynamics dominate, particles with opposite motility can obstruct each other’s movement, leading to transient dynamical arrest. This arrest can promote cluster formation and motility-induced phase separation. However, in macroscopic agents, where inertia plays a significant role, clustering is heavily influenced by bounce-back effects during collisions, which can impede cluster growth. Here we present an experiment based on active granular particles, in which inertia can be systematically tuned by changing the shaker frequency. As a result, a set of phenomena driven and controlled by inertia emerges. Before the suppression of clustering, inertia induces a transition in the cluster’s inner structure. For small inertia, clusters are characterized by the crystalline order typical of overdamped particles, while for large inertia clusters with liquid-like order are observed. In addition, in contrast to microswimmers, where active particles wet the boundary by primarily forming clusters attached to the container walls, in an underdamped inertial active system, walls do not favor cluster formation and effectively annihilate motility-induced wetting phenomena. As a consequence, inertia suppresses cluster nucleation at the system boundaries.

Exploring the local structure of molten Al-Zr-Y(Si) alloys using ab initio molecular dynamics

Accelerating the diffusion rate of Zr in aluminum and suppressing Zr segregation during solidification are crucial for enhancing the heat resistance of Al-Zr alloys. In this study, ab initio molecular dynamics simulations were employed to investigate the local structure of molten Al-Zr-Y(Si) alloys and the morphology of the liquid/substrate interface. By examining the atomic interactions, the mechanism by which Si addition improves Zr segregation during solidification and accelerates Zr diffusion was revealed. The results indicate that the interaction between Si and Zr is significantly stronger than that with other alloying elements such as Al, Y, and Zr itself. The introduction of Si had a discernible detrimental effect on Zr-Zr bonds, as Zr atoms exhibited a preference for bonding with Si atoms, consequently promoting cluster formation. This phenomenon resulted in the fragmentation of large Zr clusters into smaller ones. Moreover, the inclusion of Si atoms notably augmented the diffusion coefficient of Zr atoms within the Al-Zr-Y alloy. Analysis of the solid-liquid interface unveiled a noteworthy dragging effect, where Si atoms prominently pulled Zr atoms into the liquid phase at the interface's forefront.

Effective interactions in protein solutions with and without clustering

Protein interactions in solution and the question of cluster formation are of paramount importance to a wide range of research fields and industrial applications. Protein clustering can arise due to a delicate interplay between the short-range attraction and the long-range repulsion in the interaction potential. This study employs small angle X-ray scattering (SAXS) to examine the clustering behavior of three protein systems in solution: bovine serum albumin (BSA), bovine β-lactoglobulin (BLG) and lysozyme (LYZ) under varying protein concentrations, ionic strengths and temperatures. The goal is to elucidate the influence of the attractive potential’s nature on clustering behavior. BSA serves as a reference system, where electrostatic repulsions dominate the effective interactions, resulting in a mean protein–protein distance as a function of protein concentration which follows the 1/3 power law and precludes protein cluster formation. In contrast, BLG and LYZ solutions exhibit exponents less than 1/3, indicating concentration-dependent cluster formation. The effective interactions are well described using a two-Yukawa type potential comprising a long-ranged repulsion and a short-ranged attraction. While increasing ionic strength by adding NaCl reduced repulsion and correlation in all three systems, the response of protein solutions to ionic strength differed for clustering systems of BLG and LYZ. BLG solutions exhibited a reduced attraction with increasing ionic strength, leading to cluster dissolution, while LYZ solutions experienced enhanced attraction, favoring larger cluster formation. Notably, BLG solutions showed minimal temperature dependence, while LYZ solutions exhibited increased attraction with decreasing temperature, further promoting cluster formation. These results demonstrate the crucial role of short-ranged attractions of specific nature in determining protein clustering behavior. A thorough understanding of protein interactions is essential for predicting protein clustering and phase behavior.

Tumour immune microenvironment as the origin of heterotypic circulating tumour cell clusters and their impact on metastasis: An hypothesis

Cancer metastasis remains a significant challenge in cancer treatment, contributing to most cancer-related deaths. Circulating Tumour Cells (CTCs) are crucial for the formation of metastases, and the presence of heterotypic CTC clusters has been associated with higher metastatic potential. We hypothesize that the tumour immune microenvironment (TIME) serves as a possible site for the origin of heterotypic CTC clusters. The interactions between CTCs and non-malignant cells within the TIME can promote cluster formation, facilitate intravasation, survival in the bloodstream, and successful extravasation at secondary sites. The survival of CTCs in circulation is limited due to immune attacks and shear stress; while the formation of heterotypic clusters provides a survival advantage to CTCs by evading immune recognition. Understanding the origin and survival mechanisms of these CTC clusters in the blood is crucial for developing strategies to prevent and treat metastatic cancer. The hypothesis highlights the role of the TIME in modulating CTC behaviour and suggests that targeting tumour-associated immune cells may help disrupt CTC clusters and potentially inhibit metastasis at its early stage.

Towards a Reversible Calcium Anode through Electrolyte and Interface Engineering for Calcium Metal Batteries

Lithium-ion batteries have played an important role in decarbonizing the transportation sector, but broader utilization is currently limited by practically-attainable energy densities, safety concerns, and supply chain issues. Batteries based on calcium (Ca) metal anodes offer higher theoretical energy densities, as well as significant potential improvements in scalability and sustainability. The field of Ca metal batteries is currently in its early stages, however, due to a limited number of electrolytes that can reversibly plate and strip Ca. Two important challenges to overcome are (1) the formation of passivating solid electrolyte interphases (SEI) between Ca and the electrolyte that prevent Ca2+ transport, and (2) Ca2+-anion interactions in the electrolyte that promote cluster formation and hinder electrochemistry.1,2 This talk will explore research performed in both aspects of Ca battery development and identify strategies for future advancements. First, the electrochemical signatures of three model interfaces on Ca foil electrodes were investigated in a baseline electrolyte using cyclic voltammetry;3 the long-term cycling behavior was governed to a greater extent by electrolyte properties than the initial surface layers. Subsequent efforts have focused on electrolyte engineering, and specifically, on studying the impact that the Ca2+ coordination environment has on reversible Ca plating and stripping. For example, strong coordination between Ca2+ and the anion TFSI- has been demonstrated to deactivate Ca plating behavior via TFSI- decomposition.4,5 However, competition between coordinating molecules can be exploited to favor specific Ca2+ speciation; preferential coordination between Ca2+ and BH4 - displaces bidentate TFSI---Ca2+, unlocking Ca plating behavior in tetrahydrofuran.5 Further studies into preferential coordination are ongoing in order to better identify the connections between Ca2+ coordination, SEI formation, and anode performance. We hope to identify specific electrolyte design criteria that can advance the functionality of Ca electrolytes and ultimately examine the feasibility of Ca as a novel battery chemistry.1 Aurbach, D., Skaletsky, R. & Gofer, Y. The Electrochemical Behavior of Calcium Electrodes in a Few Organic Electrolytes. Journal of The Electrochemical Society 138, 3536-3545 (1991).2 Arroyo-de Dompablo, M. E., Ponrouch, A., Johansson, P. & Palacín, M. R. Achievements, Challenges, and Prospects of Calcium Batteries. Chemical Reviews (2019).3 Melemed, A. M. & Gallant, B. M. Electrochemical Signatures of Interface-Dominated Behavior in the Testing of Calcium Foil Anodes. Journal of The Electrochemical Society 167, 140543 (2020).4 Hahn, N. T. et al. Influence of Ether Solvent and Anion Coordination on Electrochemical Behavior in Calcium Battery Electrolytes. ACS Applied Energy Materials 3, 8437-8447 (2020).5 Melemed, A. M., Skiba, D. A. & Gallant, B. M. Toggling Calcium Plating Activity and Reversibility through Modulation of Ca2+ Speciation in Borohydride-Based Electrolytes. The Journal of Physical Chemistry C 126, 892-902 (2022).

A distinct stimulatory cDC1 subpopulation amplifies CD8+ Tcell responses in tumors for protective anti-cancer immunity.

Type 1 conventional dendritic cells (cDC1) can support Tcell responses within tumors but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8+ Tcell clustering as a unique feature of protective anti-cancer immunity. These clusters form selectively in stromal tumor regions and constitute niches in which cDC1 activate TCF1+ stem-like CD8+ Tcells. We identify a distinct population of immunostimulatory CCR7neg cDC1 that produce CXCL9 to promote cluster formation and cross-present tumor antigens within these niches, which is required for intratumoral CD8+ Tcell differentiation and expansion and promotes cancer immune control. Similarly, in human cancers, CCR7neg cDC1 interact with CD8+ Tcells in clusters and are associated with patient survival. Our findings reveal an intratumoral phase of the anti-cancer Tcell response orchestrated by tumor-residing cDC1 that determines protective versus ineffective immunity and could be exploited for cancer therapy.

The synergistic effect of organic and inorganic sulfonic acids promotes new particle formation

New particle formation (NPF) represents a significant source of aerosol particles in the atmosphere; however, the NPF mechanisms remain uncertain, hindering the understanding and assessment of its environmental effects. Hence, we investigated the nucleation mechanisms in multicomponent systems including two inorganic sulfonic acids (ISAs), two organic sulfonic acids (OSAs), and dimethylamine (DMA) by combining quantum chemical (QC) calculations and molecular dynamics (MD) simulations, and evaluated the comprehensive effect of ISAs and OSAs on DMA-driven NPF. The QC results showed that the (Acid)2(DMA)0–1 clusters were strongly stable, and the (ISA)2(DMA)1 clusters exhibited higher stability than the (OSA)2(DMA)1 clusters because ISAs (sulfuric and sulfamic acids) provided more H-bonds and stronger proton transfer than OSAs (methanesulfonic and ethanesulfonic acids). ISAs readily engaged in dimer formation, whereas the stability of trimer clusters was mainly regulated by the synergistic effects of ISAs and OSAs. OSAs participated in cluster growth earlier than ISAs. Our results revealed that ISAs promote cluster formation, whereas OSAs facilitate the growth of clusters. The synergistic effect of ISAs and OSAs should be further investigated in areas with high [OSAs]: [ISAs].

Improve Quantum Yield of Poly(Maleic Anhydride-Alt-Vinyl Acetate) via Good Solvents.

In this study, the optical properties of poly(maleic anhydride-alt-vinyl acetate) (PMV) synthesized by different polymerization methods are studied systematically. Compared to self-stabilized precipitation polymerization (pPMV), solution polymerization produces PMV solids (sPMV) with an extraordinarily high quantum yield (QY) of 20.65%. Additionally, redissolving pPMV in good solvents (rPMV) will also help to increase QY. The rising QY of sPMV and rPMV supports the idea that good solvents will reduce the rigidity of polymer chains and promote cluster formation, which is confirmed by lower glass transition temperature (Tg ) and small angle X-ray scatterer (SAXS). The study also finds that PMV exhibits application potentials in white light-emitting diodes (WLEDs) and light conversion film.

Enhanced mechanical properties in an Al-Mg-Cu alloy processed by the combination of cyclic deformation and aging heat treatment

Aging is a traditional strengthening method used for heat-treatable Al alloys. Cyclic strengthening has recently received widespread attention as a novel method for alloy strengthening. This study applied cyclic deformation to introduce dislocations and promote cluster formation in an Al-Mg-Cu alloy. Cyclically-strengthened (CS) samples have higher strength and ductility than peak-aged samples. The aging behaviors of the CS samples and the effect of pre-aging (artificial aging prior to cyclic deformation) on cyclic strengthening were also studied. Recovery and precipitation promotion were found during the aging of the CS samples regardless of pre-aging for 20 min. The pre-aged CS samples show higher strength than the CS samples without pre-aging. Interestingly, after subsequent aging, the mechanical properties of the CS samples with and without 20 min of pre-aging became the same. In summary, aging and cyclic deformation methods were combined to maximize the effects of precipitation strengthening and work-hardening. The strength limit obtained by individual aging or cyclic deformation methods was successfully overcome. This study provides new insights into alloy strengthening. • Cyclically-strengthened sample had better strength and ductility than the peak-aged sample. • Cyclic deformation promotes precipitation and leads to cluster formation. • Pre-aged samples can be cyclically strengthened due to work-hardening effects. • Enhanced mechanical properties were obtained by combining cyclic deformation and aging.

Insight into the self-aggregation behavior of lignite and anthracite in water: Atomic-level research using experiments and molecular dynamics simulations

To enable effective treatment of coal slime and prevent its release as an environmental pollutant, the interaction between coal particles in aqueous solutions must be well understood to enhance flocculation and sedimentation of the coal. In this study, the interaction between coal particles was explored using experiments and molecular simulations, which revealed the self-aggregation behavior of lignite and anthracite at different coalification levels in water. Atomic force microscopy results indicated that the anthracite–anthracite adhesion force is greater than that of lignite–lignite, and the adhesion force dominates particle interactions. The surface electrostatic potential range of lignite (-85.57–87.67 kcal/mol) is much higher than that of anthracite (-63.68–59.60 kcal/mol) and the lignite surface provides more polar regions for adsorbing water molecules. Lignite and anthracite rely on π–π accumulation to form a dimer skeleton structure. The dispersion interaction, dominated by π–π interactions, is key to promoting cluster formation and maintaining a stable cluster. The coal molecules proceed through three stages of movement, forming a cluster structure by dissipating the surrounding water molecules. The hydrophobic surface of the cluster molecules is exposed, gradually concealing the hydrophilic groups, which maintains the stability of coal self-aggregates. This process affects the water-molecule distribution, damaging the water bridge structure formed between the water molecules in coal molecule interlayers. This results in a decrease in the average number of water molecules surrounding a single lignite or anthracite molecule, and a change in the water-molecule orientation. Therefore, to enhance the flocculation of coal particles in slime water, it is necessary to increase the hydrophobicity of low-rank coal particles.

Formation and stability of the early stage solute and defect clusters in Cu-free ferritic steels during irradiation

• The mechanism of the role of specific element species in the local stability of the Mn-Ni-Si quartet clusters are investigated by DFT. • The interaction of Mn with the dumbbell interstitials is stronger than other solutes. and this is favorable for formation of the cluster. • Si can stabilize solute clusters because it forms stable covalent bonds with other solutes at 1nn. Irradiation induced significant volume fractions of Mn-Ni-Si clusters have been characterized as severe cause for the matrix embrittlement in low-Cu reactor pressure vessel steels (RPV) at high flux. The formation mechanism of these clusters is still unclear, especially when the RPV does not contain Cu. In this work, we perform density functional theory (DFT) calculations to examine the mechanism of the role of specific element species in the local stability of clusters in Fe-Mn-Ni-Si system. The binding energy of different species or configurations for quartets including Mn, Ni, Si, vacancies, and interstitial atoms is presented. Based on the DFT data, we found that point defects are more likely to promote cluster formation, and when Mn is present near the dumbbell interstitials, is favorable for formation of the cluster. Si also plays an important role by forming stable covalent bonds at 1nn to other solutes, but Si atoms cannot be close to each other because this would interfere with the magnetic properties of the surrounding Fe atoms to the extent of reducing the stability of the clusters. These results are helpful for a better understanding of the cluster formation mechanism and can provide fundamental parameters for the solute-cluster evolution with larger scale simulations.

Spontaneous assembly of redox-active iron-sulfur clusters at low concentrations of cysteine

Iron-sulfur (FeS) proteins are ancient and fundamental to life, being involved in electron transfer and CO2 fixation. FeS clusters have structures similar to the unit-cell of FeS minerals such as greigite, found in hydrothermal systems linked with the origin of life. However, the prebiotic pathway from mineral surfaces to biological clusters is unknown. Here we show that FeS clusters form spontaneously through interactions of inorganic Fe2+/Fe3+ and S2− with micromolar concentrations of the amino acid cysteine in water at alkaline pH. Bicarbonate ions stabilize the clusters and even promote cluster formation alone at concentrations >10 mM, probably through salting-out effects. We demonstrate robust, concentration-dependent formation of [4Fe4S], [2Fe2S] and mononuclear iron clusters using UV-Vis spectroscopy, 57Fe-Mössbauer spectroscopy and 1H-NMR. Cyclic voltammetry shows that the clusters are redox-active. Our findings reveal that the structures responsible for biological electron transfer and CO2 reduction could have formed spontaneously from monomers at the origin of life.

Effect of RNA on Morphology and Dynamics of Membraneless Organelles.

Membraneless organelles (MLOs) are spatiotemporally regulated structures that concentrate multivalent proteins or RNA, often in response to stress. The proteins enriched within MLOs are often classified as high-valency "scaffolds" or low-valency "clients", with the former being associated with a phase-separation promoting role. In this study, we employ a minimal model for P-body components, with a defined protein-protein interaction network, to study their phase separation at biologically realistic low protein concentrations. Without RNA, multivalent proteins can assemble into solid-like clusters only in the regime of high concentration and stable interactions. RNA molecules promote cluster formation in an RNA-length-dependent manner, even in the regime of weak interactions and low protein volume fraction. Our simulations reveal that long RNA chains act as superscaffolds that stabilize large RNA-protein clusters by recruiting low-valency proteins within them while also ensuring functional "liquid-like" turnover of components. Our results suggest that RNA-mediated phase separation could be a plausible mechanism for spatiotemporally regulated phase separation in the cell.

Self-similarity in Fluctuations and Clustering of Multiplicities

In this talk we summarize the main results of our recent publication [1], where we describe the observed by the CERN NA49 experiment a non-monotonic behavior of the fluctuations in multiplicity as a function of centrality of the collision using the concept of correlations between produced particles promoting cluster formation. A new element is a use of log-normal distribution for particles in a cluster which emerges naturally when one considers particle production based on bivariate branching scenario [2].

Fluctuations and clustering of multiplicity in collisions of relativistic ions

We discuss the recently measured event-by-event multiplicity fluctuations in relativistic heavy-ion collisions. It is shown that the observed non-monotonic behavior of the scaled variance of the multiplicity distribution as a function of collision centrality can be fully explained by the correlations between produced particles promoting cluster formation (such an effect is not observed in a widely used string-hadronic models of nuclear collisions). We define a cluster as a quasi-neutral gas of charged and neutral particles which exhibits collective behavior. The characteristic space scale of this shielding is the Debye length. The multiplicity distribution in a cluster is given by a negative binomial distribution while the rest (reservoir), treated as a superposition of elementary collisions, is described by a binomial distribution. The ability to generate spatial structures (cluster phase) with self-similar fluctuations of multiplicity sign the propensity to self-organize of hadronic matter.

Impact of anti-CASPR2 autoantibodies from patients with autoimmune encephalitis on CASPR2/TAG-1 interaction and Kv1 expression

Autoantibodies against CASPR2 (contactin-associated protein-like 2) have been linked to autoimmune limbic encephalitis that manifests with memory disorders and temporal lobe seizures. According to the growing number of data supporting a role for CASPR2 in neuronal excitability, CASPR2 forms a molecular complex with transient axonal glycoprotein-1 (TAG-1) and shaker-type voltage-gated potassium channels (Kv1.1 and Kv1.2) in compartments critical for neuronal activity and is required for Kv1 proper positioning. Whereas the perturbation of these functions could explain the symptoms observed in patients, the pathogenic role of anti-CASPR2 antibodies has been poorly studied. In the present study, we find that patient autoantibodies alter Caspr2 distribution at the cell membrane promoting cluster formation. We confirm in a HEK cellular model that the anti-CASPR2 antibodies impede CASPR2/TAG-1 interaction and we identify the domains of CASPR2 and TAG-1 taking part in this interaction. Moreover, introduction of CASPR2 into HEK cells induces a marked increase of the level of Kv1.2 surface expression and in cultures of hippocampal neurons Caspr2-positive inhibitory neurons appear to specifically express high levels of Kv1.2. Importantly, in both cellular models, anti-CASPR2 patient autoAb increase Kv1.2 expression. These results provide new insights into the pathogenic role of autoAb in the disease.

The binding property of a monoclonal antibody against the extracellular domains of aquaporin-4 directs aquaporin-4 toward endocytosis

Neuromyelitis optica (NMO), an autoimmune disease of the central nervous system, is characterized by an autoantibody called NMO-IgG that recognizes the extracellular domains (ECDs) of aquaporin-4 (AQP4). In this study, monoclonal antibodies (mAbs) against the ECDs of mouse AQP4 were established by a baculovirus display method. Two types of mAb were obtained: one (E5415A) recognized both M1 and M23 isoforms, and the other (E5415B) almost exclusively recognized the square-array-formable M23 isoform. While E5415A enhanced endocytosis of both M1 and M23, followed by degradation in cells expressing AQP4, including astrocytes, E5415B did so to a much lesser degree, as determined by live imaging using fluorescence-labeled antibodies and by Western blotting of lysate of cells treated with these mAbs. E5415A promoted cluster formation of AQP4 on the cell surface prior to endocytosis as determined by immunofluorescent microscopic observation of bound mAbs to astrocytes as well as by Blue native PAGE analysis of AQP4 in the cells treated with the mAbs. These observations clearly indicate that an anti-AQP4-ECDs antibody possessing an ability to form a large cluster of AQP4 by cross-linking two or more tetramers outside the AQP4 arrays enhances endocytosis and the subsequent lysosomal degradation of AQP4.

Stabilization of the “open” conformer of apoIscU on the surface of polystyrene nanobeads accelerates assembly of a 2Fe2S structure

AbstractThe scaffold protein IscU is involved in the assembly/transfer of FeS clusters. IscU exists in both open and closed conformation. The clusterless open conformation of IscU adheres to the hydrophobic surface of polystyrene nanobeads, as observed for other proteins. Increased accessibility of the ligand cysteines in bound IscU facilitates assembly of a 2Fe2S cluster, and the cluster-bearing structured form of IscU does not interact with the nanobeads, thus ensuring turnover. The dependence of accelerated cluster assembly on the nanobeads concentration pointed to steric and crowding effects as for promoting cluster formation, and confirms the requirement for structural flexibility of IscU .

Soil bacteria hold the key to root cluster formation.

Root clusters are bunches of hairy rootlets that enhance nutrient uptake among many plants. Since first being reported in 1974, the involvement of rhizobacteria in their formation has received conflicting support. Attempts to identify specific causative organisms have failed and their role has remained speculative. We set up a gnotobiotic experiment using two root-clustered species, Viminaria juncea (Fabaceae) and Hakea laurina (Proteaceae), and inoculated them with two plant-growth-promoting rhizobacteria (PGPR), Bradyrhizobium elkanii and Bacillus mageratium, that produce indole-3-acetic-acid (IAA). Plants were suspended in water culture with four combinations of nitrogen and phosphorus. Clusters only developed in the presence of PGPR in two treatments, were greatly enhanced in another four, suppressed in five, and unaffected in five. Nitrogen amendment was associated with a higher density of clusters. Bradyrhizobium promoted cluster formation in Hakea, whereas Bacillus promoted cluster formation in Viminaria and suppressed it in Hakea. Greater root cluster numbers were due either to a larger root system induced by PGPR (indirect resource effect) and/or to more clusters per unit length of parent root (direct morphogenetic effect). The results are interpreted in terms of greater IAA production by Bradyrhizobium than Bacillus and greater sensitivity of Viminaria to IAA than Hakea.

Dual rheological responses in Ag pastes

AbstractHighly concentrated suspensions have complex structures that complicate their characterization and study. Highly concentrated suspensions of Ag particles in ethyl cellulose solutions (Ag pastes) were thus studied and dual rheological responses were observed. Under rotational shear, the unpredicted enhancement of shear moduli occurred in the low frequency regime, showing that rheological responses of Ag pastes were strongly influenced by fillers. Under large‐amplitude oscillation, the hydrodynamic‐induced enhancement effect was observed over the whole frequency range, showing that rheological responses of Ag pastes were dominated by the binder solutions. Further studies showed that this dual behavior arose from the dual nature of structures in Ag pastes. The different shear types promoted the development of different structures in rheological experiments. Rotational shear promoted cluster formation, resulting in the unpredicted enhancement; while large‐amplitude oscillation broke the clustering, leading to the hydrodynamic enhancement. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013