Nucleation Events Research Articles

Is lactic acid a misunderstood trigger of gout attack for a century?

A gout attack could be viewed as a nucleation event. Many reports have shown that the typical molecular structure of crystallization inhibitors usually contains carboxyl and hydroxyl groups, which could interact with solute molecules through hydrogen bonding, thereby suppressing the nucleation and growth of crystals. Since 1923, l-lactic acid (LA), a molecule with structural features of inhibitors, has been speculated to be a trigger for acute gout because metabolized LA temporarily reduces uric acid excretion and leads to a slow increase in serum uric acid concentration. However, many cases of gout presumably triggered by elevated lactate in a very short period of 4 h are often inexplicable. Here, we present the unexpected result that LA has a significant “opposite effect” on the nucleation and growth of gouty pathological crystals, which is that as the concentration of the additive LA increases, the nucleation and growth of the crystals is suppressed and then facilitated. This approach may help our clarifying the long-standing “misunderstandings” and further understanding the association between metabolized LA and increased risk of gout attacks. Finally, a novel mechanism called "tailed-made occupancy (TMO)" was used to explain the nucleation and crystallization effects of LA on sodium urate monohydrate (MSUM).

Homogeneous Organic Crystal Nucleation Rates in Solution from the Perspective of Chemical Reaction Kinetics

It is demonstrated for 11 different combinations of organic solutes and solvents that the supersaturation dependence of homogeneous organic crystal nucleation rates from solution can be predicted from the solubility, bar a single empirical rate constant, when it is assumed that nucleation takes place in reversible aggregates of solvated solutes formed in supersaturated solutions. Reversible solute aggregation represents natural solute density fluctuations that take place in any solute/solvent system. For thermodynamically ideal solutions, the steady state size distribution, and thus the population of reversible aggregates in supersaturated solution, can be predicted quantitatively from the overall solute concentration by a simple mathematical expression. Supersaturation creates an excess of reversible aggregates with sizes exceeding that of the largest aggregate in saturated solution. It is shown that the number of these excess aggregates is proportional to experimental homogeneous nucleation rates, suggesting a rate equation for homogeneous nucleation that has only one empirical parameter, namely, a rate constant specific to the solute/solvent combination. This rate constant can be determined from standard nucleation rate data. The system-specificity of homogeneous nucleation rates thus appears to be encoded solely in a rate constant for the transformation of the large excess aggregates into crystal nuclei. The driving force for triggering nucleation events in these aggregates is likely the extremely high local supersaturation, which provides the conditions for spatiotemporally aligned bond-breaking (e.g., de-solvation) and bond-forming (e.g., solute–solute bonding) events that create stable crystal nuclei. The possible influence of heterogeneous nucleation by solid impurities is considered.

Delaying the First Nucleation Event of Amorphous Solid Dispersions Above the Polymer Overlap Concentration (c*): PVP and PVPVA in Posaconazole

A thorough understanding of effects of polymers on crystallization of amorphous drugs is essential for rational design of robust amorphous solid dispersion (ASD), since crystallization of the amorphous drug negates their solubility advantage. In this work, we measured the first nucleation time (t0, time to form the first critical nucleus in fresh liquid/glass) in posaconazole (POS)/polyvinylpyrrolidone vinyl acetate (PVPVA) and POS/polyvinylpyrrolidone (PVP K25) ASDs and showed that the polymer overlap concentration (c*, concentration above which adjacent polymer chains begin to contact) is critical in controlling crystallization of ASDs. When polymer concentration c < c*, t0 of POS ASDs is approximately equal to that of the neat amorphous POS, but it increases significantly when c > c*. This observation supports the view that the effective inhibitory effect of crystallization in ASDs above c* is primarily correlated with delay in the first nucleation event. Our finding is useful in efficient polymer selection and performance prediction of high drug loaded ASD formulations.

A process to reproduce repeatable 2D material-based hierarchical enhanced surface area structures

We report a repeatable method for fabrication of a 2D material-based hierarchical enhanced surface area structures (HESAS), which relies on a titanium substrate as the base for nucleation and growth and a titania-acid solution. Since the initial documentation of these formations in 2020, numerous experimental iterations have ensued, culminating in the establishment of a straightforward, replicable procedure for their fabrication. Subsequent to the inaugural report, this manuscript offers a comprehensive overview of the synthesis procedure and structural attributes. Furthermore, it summarizes various pivotal discoveries attained during the course of process refinement, including the significance of substrate preparation in particle synthesis. Specifically, the removal (or lack thereof) of the oxide layer dictates whether (or not) the 2D building blocks form, which corroborates that the composition and level of reactivity of the base surface—where the heterogenous nucleation events take root—appear to impact the ability for crystallization to occur. Nonclassical nucleation and crystallization theories could explain some of the observed patterns in the fabricated HESAS. This report briefly discusses some of the factors which affect supersaturation for the chosen synthesis system and the critical role supersaturation plays in the development of HESAS. Future work should include advancing understanding on the kinetics (and hence dynamic behavior) of the supersaturation parameters; this will be critical to develop controlled fabrication protocols of HESAS, enabling their broader adoption.

Caveolin-1 protects endothelial cells from extensive expansion of transcellular tunnel by stiffening the plasma membrane.

Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.

Caveolin-1 protects endothelial cells from extensive expansion of transcellular tunnel by stiffening the plasma membrane

Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.

Guinea fowl eggshell structural analysis at different scales reveals how organic matrix induces microstructural shifts that enhance its mechanical properties

Guinea fowl eggshells have an unusual structural arrangement that is different from that of most birds, consisting of two distinct layers with different microstructures. This bilayered organization, and distinct microstructural characteristics, provides it with exceptional mechanical properties. The inner layer, constituting about one third of the eggshell thickness, contains columnar calcite crystal units arranged vertically as in most bird shells. However, the thicker outer layer has a more complex microstructural arrangement formed by a switch to smaller calcite domains with diffuse/interlocking boundaries, partly resembling the interfaces seen in mollusk shell nacre. The switching process that leads to this remarkable second-layer microstructure is unknown. Our results indicate that the microstructural switching is triggered by changes in the inter- and intracrystalline organic matrix. During production of the outer microcrystalline layer in the later stages of eggshell formation, the interactions of organic matter with mineral induce an accumulation of defects that increase crystal mosaicity, instill anisotropic lattice distortions in the calcite structure, interrupt epitaxial growth, reduce crystallite size, and induce nucleation events which increase crystal misorientation. These structural changes, together with the transition between the layers and each layer having different microstructures, enhance the overall mechanical strength of the Guinea fowl eggshell. Additionally, our findings provide new insights into how biogenic calcite growth may be regulated to impart unique functional properties. Statement of significanceAvian eggshells are mineralized to protect the embryo and to provide calcium for embryonic chick skeletal development. Their thickness, structure and mechanical properties have evolved to resist external forces throughout brooding, yet ultimately allow them to crack open during chick hatching. One particular eggshell, that of the Guinea fowl, has structural features very different from other galliform birds – it is bilayered, with an inner columnar mineral structure (like in most birds), but it also has an outer layer with a complex microstructure which contributes to its superior mechanical properties. This work provides novel and new fundamental information about the processes and mechanisms that control and change crystal growth during the switch to microcrystalline domains when the second outer layer forms.

Transient physics in the compression and mixing dynamics of two nanochannel-confined polymer chains.

We use molecular dynamics (MD) simulation and nanofluidic experiments to probe the non-equilibrium transient physics of two nanochannel-confined polymers driven against a permeable barrier in a flow field. For chains with a persistence length P smaller than the channel diameter D, both simulation and experiment with dsDNA reveal nonuniform mixing of the two chains, with one chain dominating locally in what we term "aggregates." Aggregates undergo stochastic dynamics, persisting for a limited time, then disappearing and reforming. Whereas aggregate-prone mixing occurs immediately at sufficiently high flow speeds, chains stay segregated at intermediate flow for some time, often attempting to mix multiple times, before suddenly successfully mixing. Observation of successful mixing nucleation events in nanofluidic experiments reveal that they arise through a peculiar "back-propagation" mechanism whereby the upstream chain, closest to the barrier, penetrates and passes through the downstream chain (farthest from the barrier) moving against the flow direction. Simulations suggest that the observed back-propagation nucleation mechanism is favored at intermediate flow speeds and arises from a special configuration where the upstream chain exhibits one or more folds facing the downstream chain, while the downstream chain has an unfolded chain end facing upstream.

Insight into double twinning behavior of Mg–Gd rolled alloy at the nano scale: Role of micro-texture entropy

101¯1}− {101¯2} double twinning is a classical twinning mode with diverse variants in magnesium and its alloys. However, its variant selection criterion and its influence on the mechanical behaviors are still in debate. In this study, we proposed a view of micro-texture entropy to elucidate the double twinning behavior during large strain rolling of Mg–1.5Gd (wt%) alloy. Combined with the high spatial resolution scanning electron microscopy-transmission Kikuchi diffraction (SEM-TKD) technique, the detailed microstructure and micro-texture of the double twins in early stage of evolution were detected, and new insight into the variant selection and evolution of double twins was obtained. The observations suggest that the nucleation events of different double twin variants are influenced by their micro-texture entropy, the variants with lower micro-texture entropy are preferred. While the growth stage of double twins is affected both by their micro-texture entropy and the geometric factors between the primary and secondary twin systems; the former will influence their growth potential and the later can affect their growth space. A novel {101¯1}− {101¯3} double twin was also triggered to release the high local stress concentration during large strain rolling process.

Crystallization Inhibition in Molecular Liquids by Polymers above the Overlap Concentration (c*): Delay of the First Nucleation Event

Low concentration polymer additives can significantly alter crystal growth kinetics of molecular liquids and glasses. However, the effect of polymer concentration on nucleation kinetics remains poorly understood. Based on an experimentally determined first nucleation time (time to form the first critical nucleus, t0), we show that the polymer overlap concentration, c*, where polymer coils in the molecular liquid start to overlap with each other, is a critical polymer concentration for efficient inhibition of crystallization of a molecular liquid. The value of t0 is approximately equal to that of the neat molecular liquid when the polymer concentration, c, is below c*, but increases significantly when c > c*. This finding is relevant for effective polymer screening and performance prediction of engineered multicomponent amorphous materials, particularly pharmaceutical amorphous solid dispersions.

Identification of potential aggregation hotspots on Aβ42 fibrils blocked by the anti-amyloid chaperone-like BRICHOS domain

Protein misfolding can generate toxic intermediates, which underlies several devastating diseases, such as Alzheimer’s disease (AD). The surface of AD-associated amyloid-β peptide (Aβ) fibrils has been suggested to act as a catalyzer for self-replication and generation of potentially toxic species. Specifically tailored molecular chaperones, such as the BRICHOS protein domain, were shown to bind to amyloid fibrils and break this autocatalytic cycle. Here, we identify a site on the Aβ42 fibril surface, consisting of three C-terminal β-strands and particularly the solvent-exposed β-strand stretching from residues 26–28, which is efficiently sensed by a designed variant of Bri2 BRICHOS. Remarkably, while only a low amount of BRICHOS binds to Aβ42 fibrils, fibril-catalyzed nucleation processes are effectively prevented, suggesting that the identified site acts as a catalytic aggregation hotspot, which can specifically be blocked by BRICHOS. Hence, these findings provide an understanding how toxic nucleation events can be targeted by molecular chaperones.

A single-domain antibody detects and neutralises toxic Aβ42 oligomers in the Alzheimer’s disease CSF

BackgroundAmyloid-β42 (Aβ42) aggregation consists of a complex chain of nucleation events producing soluble oligomeric intermediates, which are considered the major neurotoxic agents in Alzheimer’s disease (AD). Cerebral lesions in the brain of AD patients start to develop 20 years before symptom onset; however, no preventive strategies, effective treatments, or specific and sensitive diagnostic tests to identify people with early-stage AD are currently available. In addition, the isolation and characterisation of neurotoxic Aβ42 oligomers are particularly difficult because of their transient and heterogeneous nature. To overcome this challenge, a rationally designed method generated a single-domain antibody (sdAb), named DesAb-O, targeting Aβ42 oligomers.MethodsWe investigated the ability of DesAb-O to selectively detect preformed Aβ42 oligomers both in vitro and in cultured neuronal cells, by using dot-blot, ELISA immunoassay and super-resolution STED microscopy, and to counteract the toxicity induced by the oligomers, monitoring their interaction with neuronal membrane and the resulting mitochondrial impairment. We then applied this approach to CSF samples (CSFs) from AD patients as compared to age-matched control subjects.ResultsDesAb-O was found to selectively detect synthetic Aβ42 oligomers both in vitro and in cultured cells, and to neutralise their associated neuronal dysfunction. DesAb-O can also identify Aβ42 oligomers present in the CSFs of AD patients with respect to healthy individuals, and completely prevent cell dysfunction induced by the administration of CSFs to neuronal cells.ConclusionsTaken together, our data indicate a promising method for the improvement of an early diagnosis of AD and for the generation of novel therapeutic approaches based on sdAbs for the treatment of AD and other devastating neurodegenerative conditions.

Textural Study of Vesicles in Tagish Lake (C2-ung) Meteorite Fusion Crust: Constraints on Vesicle Formation during Their Entry into the Earth’s Atmosphere

Vesicles are characteristic structures within the outer layer of many stony meteorites’ fusion crusts. Although these features are well-developed in hydrated carbonaceous chondrites and some micrometeorites, their formation mechanism remains poorly understood. This study provides new insights into the understanding of physical vesiculation processes by presenting the results of vesicle size distribution (VSD)—i.e., a quantitative method for vesicle analysis—applied to the study of the Tagish Lake (C2-ung) meteorite fusion crust. Tagish Lake was chosen because it shows a scoriaceous texture and a significant number of vesicles (about 24,000 vesicles/mm2), thus allowing statistical analysis. Vesicles range from being spherical to irregular-shaped and from a few μm to ~70 μm (equivalent diameter) in size. Vesicle size distribution and cumulative number density analyses show a high nucleation event and a fractal distribution of the vesicle population, respectively. We suggest these features are due to disequilibrium degassing processes, which simultaneously produce continuous/accelerating vesicle nucleation and growth. Finally, possible analogies between the scoriaceous Tagish Lake fusion crust and the space-weathered “frothy layer” on the surface of Ryugu’s grains could be found in terms of vesicularity.

Mechanical properties of amorphous CO2 hydrates: insights from molecular simulations.

Understanding physicochemical properties of amorphous gas hydrate systems is of great significance to reveal structural stabilities of polycrystalline gas hydrate systems. Furthermore, amorphous gas hydrates can occur ordinarily in the nucleation events of gas hydrate systems. Herein, the mechanical properties of amorphous carbon dioxide hydrates are examined by means of all-atom classical molecular dynamic simulations. Our molecular simulation results reveal that mechanical strengths of amorphous carbon dioxide hydrates are evidently governed by temperatures, confining pressures, and ratios of water to carbon dioxide molecules. Notably, under compressive loads, amorphous carbon dioxide hydrates firstly exhibit monotonic strain hardening, followed by an interesting distinct phenomenon characterized by a steady flow stress at further large deformation strains. Furthermore, structural evolutions of amorphous carbon dioxide hydrates are analyzed on the basis of the N-Hbond DOP order parameter. These important findings can not only contribute to our understanding of the structural stabilities of amorphous gas hydrate systems, but also help to develop fundamental understandings about grain boundaries of gas hydrate systems.

Onset of heterogeneous nucleation in pool boiling of HFE-7100 following rapid heating on a microscale heater

Effective thermal management of electronics is crucial for maintaining their reliability, longevity, and optimal performance. As electronic devices become increasingly compact and powerful, the need to explore new and innovative methods for thermal management becomes ever more critical. Rapid transitions of power lead to temperature spikes (hotspots) of up to 100 K, and thus can dramatically increase the failure occurrence of chips. Power spikes imply that heterogeneous nucleation occurs due to rapid heating, which can vary between 104 – 106 K/s, and hence the coolant is in its metastable region under various degrees of superheating. Gaining ONB data with respect to the heating rate holds significance for diverse applications including nuclear installations, engines, inkjet printers, and laser-based systems.In the present paper, we have refined the definition to a heterogeneous nucleation event due to a rapid heating process, that occurs when the timescale for the wall heating is shorter than the critical bubble’s significant growth time. Data pertaining to the dependence of the onset of nucleate boiling (ONB) on the heating rate is presented for the first time. Experiments are performed with HFE-7100 fluid that is rapidly heated using a uniquely designed micro-heater, 122 × 234 μm2 in size.The newly designed and constructed system facilitates precise measurements of fast heating processes. In this study, we conducted a series of experiments spanning heating rates from 104 to ∼106 K/s. This range of heating rates was identified in our previous studies as an intermediate regime for water. The region of intermediate heating rates was previously proved in our research to be challenging to attain, due to the varying stability of the metastable zone; it is primarily attributed to pre-existing nucleation sites. Consequently, this led to a notable gap in the experimental results for water, within this particular region, in the literature. Notably, in the current study, we were able to achieve a maximum superheating degree of 14 K at a heating rate of 2.2·106 K/s. Preheated liquids reach the same superheating degree with different heating rates, depending on the coexistence and spinodal curves. It was found that water and HFE-7100 differ significantly in their metastable zone, and that the first zone, for slower heating rates, spans approximately 12 K for water, but only 4 K for HFE-7100.

Achieving near zero-hysteretic superelasticity in a Ni43Fe18Ga27Co12 single-crystalline microwire via Lüders-like phase transformation

Ni43Fe18Ga27Co12 single-crystalline microwires directly fabricated by the Taylor liquid drawing method show the nature of a strong first-order martensitic transformation under external stress or load-biased temperature cycling. By eliminating the nucleation energy barrier through localized plastic deformation, a fully recoverable superelastic strain approaching 11 % with negligible hysteresis is achieved in the course of tensile deformation. Based on in-situ synchrotron high-energy X-ray diffraction analysis, the mechanism of nearly non-hysteretic transformation is unraveled as a sharp, Lüders-like phase transformation. It is found that a single martensitic domain propagates continuously in a monolithic fashion under superelastic cycling with poor crystallographic compatibility of λ2 = 0.950 and small volume change of ∆V = -0.17 % accompanying martensitic transformation. We attributed such near zero-hysteretic transformation characteristics to combining conditions of low crystal defect density, high nucleation barriers but without continual nucleation events, flexibility of the microwire, and small volume change.

Cooperative actin filament nucleation by the Arp2/3 complex and formins maintains the homeostatic cortical array in Arabidopsis epidermal cells.

Precise control over how and where actin filaments are created leads to the construction of unique cytoskeletal arrays within a common cytoplasm. Actin filament nucleators are key players in this activity and include the conserved actin-related protein 2/3 (Arp2/3) complex as well as a large family of formins. In some eukaryotic cells, these nucleators compete for a common pool of actin monomers and loss of one favors the activity of the other. To test whether this mechanism is conserved, we combined the ability to image single filament dynamics in the homeostatic cortical actin array of living Arabidopsis (Arabidopsis thaliana) epidermal cells with genetic and/or small molecule inhibitor approaches to stably or acutely disrupt nucleator activity. We found that Arp2/3 mutants or acute CK-666 treatment markedly reduced the frequency of side-branched nucleation events as well as overall actin filament abundance. We also confirmed that plant formins contribute to side-branched filament nucleation in vivo. Surprisingly, simultaneous inhibition of both classes of nucleator increased overall actin filament abundance and enhanced the frequency of de novo nucleation events by an unknown mechanism. Collectively, our findings suggest that multiple actin nucleation mechanisms cooperate to generate and maintain the homeostatic cortical array of plant epidermal cells.

Topology-Mediated Molecule Nucleation Anchoring Enables Inkjet Printing of Organic Semiconducting Single Crystals for High-Performance Printed Electronics.

Printable organic semiconducting single crystals (OSSCs) offer tantalizing opportunities for next-generation wearable electronics, but their development has been plagued by a long-standing yet inherent problem─spatially uncontrolled and stochastic nucleation events─which usually causes the formation of polycrystalline films and hence limited performance. Here, we report a convenient approach to precisely manipulate the elusive molecule nucleation process for high-throughput inkjet printing of OSSCs with record-high mobility. By engineering curvature of the contact line with a teardrop-shaped micropattern, molecule nucleation is elegantly anchored at the vertex of the topological structure, enabling formation of a single nucleus for the subsequent growth of OSSCs. Using this approach, we achieve patterned growth of 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene single crystals, yielding a breakthrough for an organic field-effect transistor array with a high average mobility of 12.5 cm2 V-1 s-1. These findings not only provide keen insights into controlling molecule nucleation kinetics but also offer opportunities for high-performance printed electronics.

Interactions between Gravity Waves and Cirrus Clouds: Asymptotic Modeling of Wave-Induced Ice Nucleation

Abstract We present an asymptotic approach for the systematic investigation of the effect of gravity waves (GWs) on ice clouds formed through homogeneous nucleation. In particular, we consider high- and midfrequency GWs in the tropopause region driving the formation of ice clouds, modeled with a double-moment bulk ice microphysics scheme. The asymptotic approach allows for identifying reduced equations for self-consistent description of the ice dynamics forced by GWs including the effects of diffusional growth and nucleation of ice crystals. Further, corresponding analytical solutions for a monochromatic GW are derived under a single-parcel approximation. The results provide a simple expression for the nucleated number of ice crystals in a nucleation event. It is demonstrated that the asymptotic solutions capture the dynamics of the full ice model and accurately predict the nucleated ice crystal number. The present approach is extended to allow for superposition of GWs, as well as for variable ice crystal mean mass in the deposition. Implications of the results for an improved representation of GW variability in cirrus parameterizations are discussed.

Characterizing jamming of dilute and semi-dilute fiber suspensions in a sudden contraction and a T-junction

The clogging or jamming of particle suspensions is a ubiquitous problem, hindering the efficiency of particle–liquid and particle–particle separations. Motivated by pressure screening in the pulp and paper industry, we characterize jamming of dilute and semi-dilute mono-disperse rigid-rod suspensions passing through channels mimicking dead-end and cross-flow filtration membranes, experimentally, using particle-tracking velocimetry. We observe that jams nucleate by either bridging of isolated particles across the constriction, or by localized mechanical entanglement of the particles, i.e., flocculation. Uniquely, we observe floc-formation during acceleration into the aperture and report this as primary mechanism for jamming events. We characterized the accumulation-release cycles of the jamming event using an exponential probability distribution; this distribution is indicative of a Poisson process. For jams nucleated by single-particle bridging, the distribution is (primarily) related to the number of fibers passing through the aperture; this is similar to dry, granular materials. For floc-based nucleation events, the distribution is (primarily) related to the suspension concentration with the average time between jams decreasing inversely with the square-root of the initial suspension concentration. For the conditions tested, the distribution was insensitive to changes in constriction geometry.