Monomer Loss Research Articles

Uncovering the Pathway of Serine Octamer Magic Number Cluster Formation during Electrospray Ionization: Experiments and Simulations.

Electrospray ionization (ESI) of serine (Ser) solution generates Ser8H+ as an abundant magic number cluster. ESI clustering of most other solutes yields nonspecific stoichiometries. It is unclear why Ser8H+ dominates in the case of Ser, and how Ser8H+ forms during ESI. Even the location of Ser8H+ formation is contentious (in solution, in ESI droplets, or elsewhere). Here we unravel key aspects of the l-Ser8H+ formation pathway. Harsh ion sampling conditions promote the collision-induced dissociation (CID) of regular ESI analytes. Unexpectedly, Ser8H+ was seemingly resistant against CID during ion sampling, despite its extremely low tandem mass spectrometry (MS/MS) stability. This unusual behavior reveals that Ser8H+ forms during ion sampling. We propose the following pathway: (1) Nonspecific Ser clusters are released when ESI droplets evaporate to dryness. These initial clusters cover a wide size range, from a few Ser to hundreds or thousands of monomers. (2) The clusters undergo dissociation during ion sampling, mostly via successive loss of neutral monomers. For any source activation voltage, there is a subpopulation of clusters for which this CID cascade tends to terminate at the octamer level, culminating in Ser8H+-dominated product distributions. Mobile proton molecular dynamics simulations were used to model the entire pathway. Ser8H+ structures formed in these simulations were consistent with ion mobility experiments. The most compact structures resembled the model of [Scutelnic, V. J. Am. Chem. Soc. 2018, 140, 7554-7560], with numerous intermolecular salt bridges and H-bonds. Our findings illustrate how the interplay of association and dissociation reactions across phase boundaries can culminate in magic number clusters.

Formation mechanism of α particles in glycogen: Testing the budding hypothesis by Monte-Carlo simulation

Glycogen, a complex branched glucose polymer and a blood-sugar reservoir in animals, comprises small β particles joined together into composite α particles. In diabetic animals, α particles fragment more easily than those in healthy animals. Finding evidence for or against postulated mechanisms for α-particle formation is thus important for diabetes research. Insight into this is obtained here using Monte-Carlo simulations, including addition and loss of glucose monomer, branching and debranching, based on earlier simulations which were in acceptable agreement with experiment [Zhang et al., Int J Biol Macromolecules 2018, 116, 264]. One postulated mechanism for α-particle formation is “budding”: occasionally a glucan chain temporarily protrudes from the particle, and if its growing end is sufficiently far from its parent particle, it propagates to a new linked particle. We tested this by simulations in which an “artificial” bud (a chain extending well outside the average particle radius) is added to a glycogen molecule in a dynamic steady state, and the system allowed to evolve. In some simulations, the particle reached a new steady state having an irregular dumbbell shape: a rudimentary α particle. Thus ‘budding’ is a possible mechanism for α particles to form. If no simulations had shown this behaviour, it would have refuted the postulate.

Application of singular value decomposition analysis: Insights into the complex mechanisms of amyloidogenesis

Amyloidogenesis, with its multifaceted nature spanning from peptide self-assembly to membrane-mediated structural transitions, presents a significant challenge for the interdisciplinary scientific community. Here, we emphasize on how Singular Value Decomposition (SVD) can be employed to reveal hidden patterns and dominant modes of interaction that govern the complex process of amyloidogenesis. We first utilize SVD analysis on Circular Dichroism (CD) spectral datasets to identify the intermediate structural species emerging during peptide-membrane interactions and to determine binding constants more precisely than conventional methods. We investigate the monomer loss kinetics associated with peptide self-assembly using Nuclear Magnetic Resonance (NMR) dataset and determine the global kinetic parameters through SVD. Furthermore, we explore the seeded growth of amyloid fibrils by analyzing a time-dependent NMR dataset, shedding light on the kinetic intricacies of this process. Our analysis uncovers two distinct states in the aggregation of Aβ40 and pinpoints key residues responsible for this seeded growth. To strengthen our findings and enhance their robustness, we validate those using simulated data, thereby highlighting the physical interpretations derived from SVD. Overall, SVD analysis offers a model-free, global kinetic perspective, enabling the selection of optimal kinetic models. This study not only contributes valuable insights into the dynamics but also highlights the versatility of SVD in unravelling complex processes of amyloidogenesis.

Understanding the impact of mannitol on physical stability and aerosolization of spray-dried protein powders for inhalation

Pulmonary delivery of protein-based therapeutics, including antibodies, is a promising option for treating respiratory diseases. Spray drying is a widely used method for producing dry powder formulations with mannitol being a commonly used excipient for these inhalation formulations. There is limited research available concerning the utilization of mannitol as an excipient in the spray drying of proteins and its impact on aerosol performance. This study highlights the importance to understand mannitol’s potential role and impact in this context. To investigate the impact of mannitol on physical stability and aerosolization of spray-dried protein formulations, bovine serum albumin (BSA) was employed as a model protein and formulated with different concentrations of mannitol via spray drying. The spray-dried solids were characterized for their particle size using Malvern mastersizer and aerodynamic particle size using next generation impactor (NGI). Additionally, the solids were characterized with solid-state Fourier-transform infrared spectroscopy (ssFTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and solid-state nuclear magnetic resonance spectroscopy (ssNMR) to analyze the change in their secondary structure, crystallinity, particle morphology, and protein-excipient interaction, respectively. Size exclusion chromatography (SEC) was used to investigate changes in monomer content resulting from storage under stressed condition of 40 °C. Protein formulations containing more than 33 % mannitol by weight showed crystallization tendencies, causing an increase in monomer loss over time. ssNMR data also showed mixing heterogeneity of BSA and mannitol in the formulations with high mannitol contents. Futhermore, fine particle fraction (FPF) was found to decrease over time for the formulations containing BSA: Mannitol in the ratios of 2:1, 1:2, and 1:5, due to particle agglomeration induced by crystallization of mannitol. This study underscores the significant influence of excipients such as mannitol on the aerosol performance and storage stability of spray-dried protein formulations.

Enhancement of thermal and mechanical properties of microencapsulated phase change materials with graphene oxide

The low thermal conductivity of microencapsulated phase change materials (MEPCMs) limits the latent heat charging and discharging rates for various applications. To overcome this limitation, we prepared MEPCM by co-surfactants of polyvinyl alcohol and high thermal conductivity graphene oxide (GO) through an emulsion polymerization process. Fourier transformation infrared spectroscopy and Raman spectra results verified that GO was successfully added to the MEPCMs' hybrid polymer shell. The core material content of MEPCM and GO/MEPCM was within the range of 78.4 %−91.8 % according to differential scanning calorimetry testing results. According to the comparison of fabricated microcapsule samples, the dosage of 0–0.5 w.t.% GO can reduce the loss of shell monomers and overcome the supercooling and leakage problem of MEPCM. Thermogravimetric results exhibited that the thermal stability of MEPCM samples increased by 66 °C after encapsulation, and this value further increased by 7–21 °C with the addition of 0.1–0.5 w.t.% GO. The thermal conductivity of MEPCM samples increased from 0.32 W/m∙K to 1.04 W/m∙K with a dosage of 0.5 w.t.% GO. Meanwhile, Young's modulus and the hardness of GO/MEPCM samples with 0.5 w.t.% GO increased by 0.2 GPa and 0.1 GPa, respectively.

Evaluation of laboratory and environmental exposure systems for protein modification upon gas pollutants and environmental factors

Chemical modifications of proteins induced by ambient ozone (O3) and nitrogen oxides (NOx) are of public health concerns due to their potential to trigger respiratory diseases. The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere. Using bovine serum albumin (BSA) as a model protein, we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study. In the laboratory simulation system, the generated gaseous pollutants showed negligible losses. Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%. For environmental exposure experiment, quartz fiber filter was selected as the upper filter with low gaseous O3 (8.0%) and NO2 (1.7%) losses, and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%. The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions, while environmental factors (e.g., molecular oxygen and ultraviolet) may cause greater protein monomer losses. Based on the evaluation, the study exemplarily applied the two systems to protein modification and both showed that O3 promotes the protein oligomerization and nitration, while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples. The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions. A combination of the two will further reveal the actual mechanism of protein modifications.

Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development.

Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss consistently attenuates the relative retrotransposition potential of their offspring (daughter) L1 insertions. We also observe that most donor/daughter L1 pairs are efficiently methylated upon differentiation in vivo and in vitro. We use Oxford Nanopore Technologies (ONT) long-read sequencing to resolve L1 methylation genome-wide and at individual L1 loci, revealing a distinctive "smile" pattern in methylation levels across the L1 promoter region. Using Pacific Biosciences (PacBio) SMRT sequencing of L1 5' RACE products, we then examine DNA methylation dynamics at the mouse L1 promoter in parallel with transcription start site (TSS) distribution at locus-specific resolution. Together, our results offer a novel perspective on the interplay between epigenetic repression, L1 evolution, and genome stability.

Solid-Solid Interfacial Contact of Tubing Walls Drives Therapeutic Protein Aggregation During Peristaltic Pumping

Peristaltic pumping during bioprocessing can cause therapeutic protein loss and aggregation during use. Due to the complexity of this apparatus, root-cause mechanisms behind protein loss have been long sought. We have developed new methodologies isolating various peristaltic pump mechanisms to determine their effect on monomer loss. Closed-loops of peristaltic tubing were used to investigate the effects of peristaltic pump parameters on temperature and monomer loss, whilst two mechanism isolation methodologies are used to isolate occlusion and lateral expansion-relaxation of peristaltic tubing. Heat generated during peristaltic pumping can cause heat-induced monomer loss and the extent of heat gain is dependent on pump speed and tubing type. Peristaltic pump speed was inversely related to the rate of monomer loss whereby reducing speed 2.0-fold increased loss rates by 2.0- to 5.0-fold. Occlusion is a parameter that describes the amount of tubing compression during pumping. Varying this to start the contacting of inner tubing walls is a threshold that caused an immediate 20-30% additional monomer loss and turbidity increase. During occlusion, expansion-relaxation of solid-liquid interfaces and solid-solid interface contact of tubing walls can occur simultaneously. Using two mechanisms isolation methods, the latter mechanism was found to be most destructive and a function of solid-solid contact area, where increasing the contact area 2.0-fold increased monomer loss by 1.6-fold. We establish that a form of solid-solid contact mechanism whereby the contact solid interfaces disrupt adsorbed protein films is the root-cause behind monomer loss and protein aggregation during peristaltic pumping.

Effect of Atomic Layer Coating on the Stability of Solid Myoglobin Formulations.

The effects of atomic layer (ALC) coating on physical properties and storage stability were examined in solid powders containing myoglobin, a model protein. Powders containing myoglobin and mannitol (1:1 w/w) were prepared by lyophilization or spray drying and subjected to aluminum oxide or silicon oxide ALC coating. Uncoated samples of these powders as well as coated and uncoated samples of myoglobin as received served as controls. After preparation (t0), samples were analyzed for moisture content, reconstitution time, myoglobin secondary structure, crystallinity, and protein aggregate content. Samples were stored for 3 months (t3) under controlled conditions (53% RH, 40 °C) in both open and closed vials and then analyzed as above. At t3, the recovery of soluble native (i.e., monomeric) protein depended on formulation, coating type, and drying method and was up to 2-fold greater in coated samples than in uncoated controls. Promisingly, some samples with high recovery also showed low soluble aggregate content (<10%) at t3 and low total monomer loss; the latter was correlated to sample moisture content. Overall, the results demonstrate that ALC coatings can stabilize solid protein formulations during storage, providing benefits over uncoated controls.

Temporal control by cofactors prevents kinetic trapping in retroviral Gag lattice assembly

For retroviruses like HIV to proliferate, they must form virions shaped by the self-assembly of Gag polyproteins into a rigid lattice. This immature Gag lattice has been structurally characterized and reconstituted in vitro, revealing the sensitivity of lattice assembly to multiple cofactors. Due to this sensitivity, the energetic criterion for forming stable lattices is unknown, as are their corresponding rates. Here, we use a reaction-diffusion model designed from the cryo-ET structure of the immature Gag lattice to map a phase diagram of assembly outcomes controlled by experimentally constrained rates and free energies, over experimentally relevant timescales. We find that productive assembly of complete lattices in bulk solution is extraordinarily difficult due to the large size of this ∼3700 monomer complex. Multiple Gag lattices nucleate before growth can complete, resulting in loss of free monomers and frequent kinetic trapping. We therefore derive a time-dependent protocol to titrate or “activate” the Gag monomers slowly within the solution volume, mimicking the biological roles of cofactors. This general strategy works remarkably well, yielding productive growth of self-assembled lattices for multiple interaction strengths and binding rates. By comparing to the in vitro assembly kinetics, we can estimate bounds on rates of Gag binding to Gag and the cellular cofactor IP6. Our results show that Gag binding to IP6 can provide the additional time delay necessary to support smooth growth of the immature lattice with relatively fast assembly kinetics, mostly avoiding kinetic traps. Our work provides a foundation for predicting and disrupting formation of the immature Gag lattice via targeting specific protein-protein binding interactions.

High Pressure Light Scattering of Therapeutic Proteins To Probe Aggregation and Protein-Protein Interactions.

There is interest in the direct in situ measurement of protein aggregation and reversible protein-protein interactions at high pressure as a means to assess protein stability. This is currently limited by the availability of in-house analytical methods. High-pressure (HP) scattering instrumentation (using either neutrons, X-rays, or light sources) are relatively rare, due to extensive development hurdles and lack of standardization. This report focuses on design, operation, and application of a new HP light scattering apparatus based on commercially available equipment with a view to wider applications. HP static light scattering results were obtained for two monoclonal antibodies (MAbs) that exhibit different extents of unfolding and aggregation at these conditions. Aggregation that was observed during in situ pressure incubations varied by MAb and total ionic strength of solution. This was conducted in tandem with ex situ measurements on MAb solutions that were incubated under pressure, where monomer loss was measured with size exclusion chromatography. Pressure cycling was also used to assess the extent of pressure-induced reversible and irreversible aggregation. Finally, the ability of the HP light scattering apparatus to assess the influence of pressure on reversible protein-protein interactions in the canonical sense of second osmotic virial coefficients was assessed using lysozyme, a relatively well-characterized protein under hydrostatic pressure. The method offers a convenient and reproducible capability that complements current small angle neutron/X-ray instrumentation, providing measurements that can be used to optimize the planning and interpretation of scattering data from synchrotron or neutron research facilities. Our results address a growing demand to characterize protein aggregates and aggregation-prone partially unfolded intermediates.

Development of a stepwise solvent-gradient SMB process for continuous-mode purification of methoxyethyl nucleoside phosphoramidites to be used as the key building blocks of oligonucleotide drugs

One of the commercially proven oligonucleotide-based drugs that can treat a variety of life-threatening diseases through gene-expression control is 2′-O-methoxyethyl (MOE) oligonucleotide. To keep the economical production of the MOE-oligonucleotide stable, it is important to establish an efficient process for recovering its corresponding monomer (MOE nucleoside phosphoramidites) in a large quantity at high purity from the output of the phosphitylation reaction based on using MOE nucleoside as a starting component. To address this issue, we pursued the development of an efficient simulated-moving-bed (SMB) process for continuous-mode recovery of monomer from the considered reaction output. First, the intrinsic parameters of monomer and impurities present in the reaction output were obtained through an inverse method using silica gel as an adsorbent. The resulting intrinsic parameters were then applied to the optimal design of the SMB process for monomer recovery, which revealed that its optimal configuration was a four-zone open-loop SMB configuration based on the installation of regeneration and re-equilibration zones for implementing a stepwise solvent-gradient method. Under such configuration, the optimal SMB operation parameters to maximize throughput while keeping high purity stable were determined using the relevant optimization tool based on column model and genetic algorithm. It was confirmed through the experimental run that the optimized SMB process could enable the continuous recovery of monomer from the considered reaction output with 99.6% purity while keeping the monomer loss close to zero. Finally, the developed SMB process in this article was found to increase throughput by more than 33 times, and reduce solvent usage by more than 89%, compared to the plant-scale batch chromatographic process currently in operation in related industries.

Agarose native gel electrophoresis analysis of thermal aggregation controlled by Hofmeister series

The effects of salting-in and salting-out salts defined by Hofmeister series on the solution state of bovine serum albumin (BSA) in 50 mM Tris-HCl buffer at pH 7.4 before and after thermal unfolding at 80 °C for 5 min were examined using agarose native gel electrophoresis and mass photometry. Gel electrophoresis showed that salting-in MgCl2, CaCl2 and NaSCN resulted in formation of intermediate structures of BSA upon heating on native gel, while heating in buffer alone resulted in aggregated bands. Mass photometry showed large loss of monomer and oligomers when heated in this buffer, but retaining these structures in the presence of 1 M MgCl2 and NaSCN. To our surprise, salting-out MgSO4 also showed a similar effect on gel electrophoresis and mass photometry. Salting-out NaCl and (NH4)2SO4 resulted in smearing and aggregated bands, which were supported by mass photometry. Aggregation-suppressive ArgHCl also showed oligomer aggregates upon gel electrophoresis and mass photometry.

Rational Design and Production of Bioactive Analogs of Recombinant Human Keratinocyte Growth Factor (rhKGF) with Reduced Aggregation Propensity.

Recombinant human keratinocyte growth factor (rhKGF) is a highly aggregation-prone therapeutic protein. The present study aimed to reduce aggregation propensity of rhKGF by engineering the aggregation hotspots. Initially, 21 mutants were designed based on the previously-identified aggregation-prone regions (APRs) and then four of them including mutants No. 4 (L91K, I119K), 7 (V13S, L91K), 14 (L91D, I119D), and 21 (A51E) were selected based on molecular dynamics (MD) simulations for further experimental studies. The recombinantly produced rhKGF and mutants were analyzed regarding secondary structure, thermal stability, aggregation propensity, and biological activity. Far-UV CD spectroscopy showed that the mutants have similar secondary structure with rhKGF. A51E mutant showed enhanced stability and decreased monomer loss under heat stress suggesting its reduced aggregation propensity compared to rhKGF. Mutant No. 14 showed higher stability and less aggregation tendency than mutant No. 4 indicating that only mutations decreasing pI of rhKGF are effective in reducing its aggregation tendency. All of the mutants were at least as potent as rhKGF in stimulating proliferation of MCF-7 epithelial cells. Our results identified A51E as an equally potent, more stable, and less aggregation-prone analog of rhKGF which could be a promising alternative drug candidate for the commercially available rhKGF (Palifermin).

Electrochemical Analysis in Studying β-Amyloid Aggregation.

β-amyloid (Aβ) is comprised of a group of peptides formed as a result of cleavage of the amyloid precursor protein by secretases. Aβ aggregation is considered as a central event in pathogenesis of Alzheimer's disease, the most common human neurodegenerative disorder. Molecular mechanisms of Aβ aggregation have intensively being investigated using synthetic Aβ peptides by methods based on monitoring of aggregates, including determination of their size and structure. In this review, an orthogonal approach to the study of Aβ aggregation is considered, which relies on electrochemical registration of the loss of peptide monomers. Electrochemical analysis of Aβ (by voltammetry and amperometric flow injection analysis) is based on registration of the oxidation signal of electroactive amino acid residues of the peptide on an electrode surface. The Aβ oxidation signal disappears, when the peptide is included in the aggregate. The advantages and disadvantages of electrochemical analysis for the study of spontaneous and metal-induced aggregation of Aβ, comparative analysis of various peptide isoforms, and study of the process of complexation of metal ions with the metal-binding domain of Aβ are discussed. It is concluded that the combined use of the electrochemical method and the methods based on detection of Aβ aggregates makes it possible to obtain more complete information about the mechanisms of peptide aggregation.

Reduction of dielectric loss of ethylene propylene diene monomer (EPDM) with high barrier graphene (HBG) modified by heptadecafluoro-decyl-triethoxy silane

Reduction of dielectric loss of ethylene propylene diene monomer (EPDM) with high barrier graphene (HBG) modified by heptadecafluoro-decyl-triethoxy silane

Multi-Level High-Throughput Screening for Discovery of Ligands That Inhibit Insulin Aggregation.

We have developed a multi-level virtual screening protocol to identify lead molecules from the FDA inactives database that can inhibit insulin aggregation. The method is based on the presence of structural and interaction specificity in non-native aggregation pathway protein-protein interactions. Some key challenges specific to the present problem, when compared with native protein association, include structural heterogeneity of the protein species involved, multiple association pathways, and relatively higher probability of conformational rearrangement of the association complex. In this multi-step method, the inactives database was first screened using the dominant pharmacophore features of previously identified molecules shown to significantly inhibit insulin aggregation nucleation by binding to its aggregation-prone conformers. We then performed ensemble docking of several low-energy ligand conformations on these aggregation-prone conformers followed by molecular dynamics simulations and binding affinity calculations on a subset of docked complexes to identify a final set of five potential lead molecules to inhibit insulin aggregation nucleation. Their effect on aggregation inhibition was extensively investigated by incubating insulin under aggregation-prone aqueous buffer conditions (low pH, high temperature). Aggregation kinetics were characterized using size exclusion chromatography and Thioflavin T fluorescence assay, and the secondary structure was determined using circular dichroism spectroscopy. Riboflavin provided the best aggregation inhibition, with 85% native monomer retention after 48 h incubation under aggregation-prone conditions, whereas the no-ligand formulation showed complete monomer loss after 36 h. Further, insulin incubated with two of the screened inactives (aspartame, riboflavin) had the characteristic α-helical dip in CD spectra, while the no-ligand formulation showed a change to β-sheet rich conformations.

Dynamics of semiflexible generalized scale-free polymer networks

We study the relaxation dynamics of a new type of hyperbranched polymer networks, which are constructed using a degree distribution specific to scale-free networks. The topology of the constructed networks is controlled through three parameters: γ, which measures the density of links in the network, the minimum allowed degree Kmin and the maximum allowed degree Kmax. The static properties of the polymers are investigated through the mean square radius of gyration. We study the dynamics in the framework of the generalized Gaussian structures model by monitoring in detail the influence of networks’ construction parameters, namely γ, Kmin, and Kmax, and the stiffness parameter q on the relaxation quantities: averaged monomer displacement, storage modulus and loss modulus. In the intermediate (time or frequency) regions of the dynamical quantities we encounter a scaling behavior for γ=2.5 and usually a non-scaling behavior for other values of γ. Switching on the stiffness parameter q one is able to destroy, create or enlarge some scaling regions for other combinations of the parameters. Another way to widen a scaling region is to slightly increase Kmin.

Preparation of anthocyanin-rich mulberry juice by microwave-ultrasonic combined pretreatment.

The work aims to study the process of microwave-ultrasonic combined treatment to obtain anthocyanin-rich mulberry juice. A Box-Behnken design was employed to analyze the effects of microwave time and citric acid content on the total phenol content, total anthocyanin content, hue, color intensity, DPPH and ABTS radical scavenging activities. Under the optimum conditions (microwave time of 46s, citric acid addition of 273mg/kg), the total phenol content, total anthocyanin content, the DPPH and ABTS radical scavenging activities reached 4.24mg GAE/mL, 3.29mg C3G/mL, 4.59mg TE/mL and 11.90mg TE/mL, respectively. Subsequently, the mulberry juice was processed with ultrasound of different frequencies. It was found that low-frequency ultrasonic treatment (25kHz) could significantly reduce the loss of total phenolic and anthocyanin monomers and improve the antioxidant capacity of mulberry juice during storage for five weeks. Overall, mulberry juice with microwave-ultrasonic pretreatment is a natural antioxidant.

Oscillations in a Becker--Döring Model with Injection and Depletion

We study the Becker--Döring bubblelator, a variant of the Becker--Döring coagulation-fragmentation system that models the growth of clusters by gain or loss of monomers. Motivated by models of gas evolution oscillators from physical chemistry, we incorporate the injection of monomers and depletion of large clusters. For a wide range of physical rates, the Becker--Döring system itself exhibits a dynamic phase transition as mass density increases past a critical value. We connect the Becker--Döring bubblelator to a transport equation coupled with an integrodifferential equation for the excess monomer density by formal asymptotics in the near-critical regime. For suitable injection/depletion rates, we argue that time-periodic solutions appear via a Hopf bifurcation. Numerics confirm that the generation and removal of large clusters can become desynchronized, leading to temporal oscillations associated with bursts of large-cluster nucleation.