Physics of Fluids
● AIP Publishing
Preprints posted in the last 90 days, ranked by how well they match Physics of Fluids's content profile, based on 13 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.
Ahmed, M.; Akerkouch, L.; Haage, A.; Le, T. B.
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This work presents the development of a novel approach to model the dynamics of cancer cells in microcirculation. We investigate the role the membrane elasticity, and cancer cell shape on deformation dynamics under the shear and pressure forces in a micro-channel. The proposed numerical model is based on a hybrid continuum-particle approach. The cancer cell model includes the cell membrane, nucleus, cytoplasm and the cytoskeleton. The Dissipative Particle Dynamics method was employed to simulate the mechanical components. The blood plasma is modeled as a Newtonian incompressible fluid. A Fluid-Structure Interaction coupling, leveraging the Immersed Boundary Method is developed to simulate the cells response to flow dynamics. We quantify how subtle variations in these biophysical properties alter deformation indices such as sphericity and aspect ratio, and stress distributions on the membrane of the cancer cell. Our findings align well with existing computational and experimental studies. Results reveal that increased membrane stiffness reduces overall deformation as well as the total distance traveled. Similarly, cell geometry strongly influences flow-structure interactions: near-spherical morphologies exhibit stable deformation with minimal sensitivity to shear variations, whereas elongated geometries show pronounced orientation and stretching effects. Collectively, these findings highlight the critical importance of cell-specific heterogeneity in governing cell dynamics in microvascular flows. Furthermore, the intracellular and extracellular dynamics response of the cancer cell are intrinsically linked to their shape, in which certain morphologies displayed strong resistance to the fluid-induced forces and the ability to migrate in various directions. The insights obtained provide a mechanistic framework for understanding circulating tumor cell transport in shear-dominated environments during metastasis. Our work may inform the design of biomimetic microfluidic systems and therapeutic strategies targeting cancer cell detection and cancer prognosis.
Sinzato, Y. Z.; Verspagen, J. M. H.; Uittenbogaard, R.; Visser, P. M.; Huisman, J.; Jalaal, M.
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Cyanobacterial colonies often exploit their buoyancy and large size to float upwards rapidly and form dense surface blooms, which can degrade water quality, threaten ecosystems and public health, and impose substantial economic costs. Yet, how the morphology of cyanobacterial colonies controls their vertical velocity remains poorly understood. We conducted detailed three-dimensional morphological characterization of colonies of the cyanobacterium Microcystis in lake samples at the single-colony level and performed controlled flotation experiments in stratified flows. Using particle tracking in a vertical density gradient, we separately quantified the contributions of colony shape and buoyant density at the level of individual colonies. Our results show that the shape factor in Stokes law varies systematically with colony size. Consequently, the vertical velocity of colonies does not scale with the square of colony size but only with a power of 1.13, as larger colonies have a more irregular shape and therefore experience enhanced drag. We therefore correct the commonly used Stokes law to account for the size-dependent change in the shape factor. Interestingly, implementation of this power law relationship in a vertical migration model shows widespread chaotic dynamics in the migration trajectories of Microcystis colonies. These results highlight the importance of morphological plasticity in cyanobacterial colonies and can inform predictive models and hydrodynamic control strategies for toxic blooms. Our methodology to simultaneously determine the density, shape factor and velocity is broadly applicable to suspended aggregates with complex shapes in freshwater and marine systems.
Ahmed, M.; Akerkouch, L.; Vanyo, A.; Haage, A.; Le, T. B.
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PurposeThis work investigates the role of the cancer cell morphology and elasticity on the deformation patterns under shear-flow in a micro-channel. MethodsA novel hybrid continuum-particle framework is developed to simulate cancer-cell dynamics. Cell membrane and nucleus geometries are reconstructed from microscopic images and modeled using Dissipative Particle Dynamics, while the surrounding blood plasma is treated as an incompressible Newtonian fluid. Cell-flow interactions are captured via an immersed boundary method. ResultsAll cancer-cell models exhibited a rapid deformation response within the first 1-2 ms, followed by morphology- and stiffness-dependent shape evolution. The compact morphologies showed strong recovery, whereas the other models evolved toward folded/lobed states with only intermittent partial recovery during shape transitions. Membrane stiffening dominated elongation and compactness loss, while nuclear stiffening modulated deformation excursions and partial recovery. These shape transitions were accompanied by near-field vortex reorganization and traction localization. Similar to deformation response the net membrane force exhibited a common start-up rise within 0-0.5 ms followed by relaxation. Compact morphologies produce lower and steadier forces. They show minimal stiffness dependence. Deformation-prone morphologies show stronger unsteadiness and clearer stiffness modulation. Cross-sectional velocity and vorticity fields showed a dominant x-directed hydrodynamic imbalance and lateral migration. ConclusionOur results demonstrate that morphology sets the stiffness modulated deformation patterns which effects the extracellular flow dynamics and traction. In turn, the resulting flow field and traction distribution feed back to influence subsequent deformation and migration. This mechanistic link provides a framework for interpreting circulating tumor cell transport in shear-dominated metastatic environments.
Calicchia, M. A.; Ni, R.
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Despite its ubiquity in natural flows, the effects of turbulence on fish locomotion and behavior remain poorly understood. The prevailing hypothesis is that these effects depend on the spatial and temporal scales of the turbulence relative to the fishs size and swimming speed. But in conventional facilities, turbulence usually increases with mean flow, which forces higher swimming speeds and can leave these relative scales unchanged. We therefore present a novel experimental facility that leverages a jet array to decouple the turbulence from the mean flow and systematically control its scales. This approach allows the ratio of turbulent to fish inertial scales to be varied over an order of magnitude, providing a controlled framework for quantifying fish-turbulence interactions. The facility also supports experiments probing strategies fish may use to cope with turbulence, including collective behaviors. Insights from this work have broader implications for ecological studies and engineering applications, including the design of effective fishways and bio-inspired underwater vehicles.
Dvoriashyna, M.; Zwanenburg, J. J. M.; Goriely, A.
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Cerebrospinal fluid (CSF) is a Newtonian fluid that bathes the brain and spinal cord and oscillates in response to the physiological periodic changes in brain volume, of which the cardiac cycle is a major driver. Understanding this motion is essential for clarifying its contribution to solute transport, waste clearance, and drug delivery. In this work, we study oscillatory and steady streaming flow in the cranial subarachnoid space using a lubrication-based theoretical framework. The model represents the cranial CSF compartment as a thin fluid layer bounded internally by the brain surface and externally by the dura, driven by time-dependent brain surface displacements. We first derive simplified governing equations for flow over an arbitrary smooth sphere-like brain surface and obtain analytical solutions for an idealised spherical geometry with uniform displacements. We then incorporate realistic displacement fields reconstructed from MRI measurements in healthy subjects and solve the reduced equations numerically. The results show that oscillatory forcing produces a steady streaming component that may enhance solute transport compared with diffusion alone. This work provides a mechanistic description of the flow generated by physiological brain motion and highlights the potential presence of steady streaming in cranial subarachnoid fluid dynamics.
Zhang, Z.; Yi, H.; Kolanjiyil, A. V.; Liu, C.; Feng, Y.
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Small airways are the primary sites of airflow obstruction in chronic obstructive pulmonary disease. Effective delivery of aerosolized drug particles to these regions is crucial to maximize treatment efficacy while minimizing side effects. However, conventional inhalation therapy approaches (i.e., full-mouth particle release and inhalation (FMD)) typically result in insufficient drug deposition in the small airways and an uneven distribution across the five lung lobes. To address such deficiencies, the goals of this study are triple folds: (1) to develop a fast and accurate framework to secure target drug delivery (TDD) nozzle diameter and location based on the conventional computational fluid particle dynamics (CFPD)-FMD simulations, (2) to develop a CFPD-informed machine learning (ML) inverse-design framework that predicts optimal inhaler nozzle parameters based on patient-specific breathing patterns and drug properties, and (3) to demonstrate the feasibility of embedding this framework into a user-centered smart inhaler prototype to improve uniform TTD to the small airways across all five lung lobes. Specifically, a subject-specific mouth-to-generation-10 human respiratory system was employed, and 108 high-fidelity CFPD-FMD simulations were performed under varied physiological and design parameters, including tidal volume, particle diameter, release location, and release timing. Particle release maps generated from those CFPD-FMD simulations via backtracking identified optimal nozzle diameters and locations that promote uniform multi-lobe drug delivery while limiting off-target deposition. Accordingly, a dataset was compiled with inputs (i.e., flow rate, particle size, release z-coordinate, release time) and targets (i.e., nozzle center x- and y-coordinates, nozzle diameter). These inputs and targets form the CFPD-TDD dataset, on which 16 ML models were trained to learn inverse mapping from patient- and drug-specific inputs to optimal nozzle design parameters. Performance was evaluated using mean squared error (MSE) and mean absolute error (MAE) overall and per target feature. Parametric analysis using CFPD-FMD simulations was conducted to determine how patient-specific and drug-specific factors affect pulmonary air-particle transport dynamics and to explain why achieving CFPD-TDD in small airways with CFPD-FMD strategies remains challenging. Furthermore, the ML evaluation in this feasibility study demonstrated robust learning of the inverse mapping from patient-specific inputs to optimal nozzle parameters. Four top-performing models showed consistently low MSE/MAE across cases, and an ensemble (i.e., mixed model (MixModel)) combining their strengths was formulated. Independent CFPD-TDD simulations beyond the training and testing datasets were used as the ground truth to validate ML-predicted nozzle configurations. Compared with conventional CFPD-FMD strategies, ML-guided nozzle designs significantly improved inter-lobar deposition uniformity and reduced off-target deposition in the upper airways, demonstrating the feasibility of ML-enabled TDD to the small airways. Overall, this study establishes a CFPD-informed ML inverse-design framework as a viable algorithmic foundation for user-centered smart inhalers, enabling adaptive, patient-specific TDD to the small airways with improved deposition uniformity across all five lung lobes. By integrating first-principle-based CFPD with ML, this work provides a methodological pathway toward next-generation smart inhalers for more effective treatment of small airway diseases.
Soman, P.; Poudel, A.; Limjuico, J. E. N.; Aryal, U.; Hossain, M. T.; Basu, S.
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Currently in vitro models of microvascular biology rely on self-assembly of vascular cells in compatible gels. However, the stochastic nature of this process results in large variations in lumen sizes, perfusion continuity, and shear stresses making systematic and reproducible analysis challenging. Here, we report a new technology to generate artificial capillaries on a chip with custom control over lumen sizes and architectures using a combination of femtosecond laser cavitation and collagen casting within multi-chambered microfluidic chips. The design allows seeding of endothelial cells within capillary-sized microchannels and seeding of stromal cells within top-open silos, with independent control over seeding sequence and media compositions. Results show that endothelialized microchannels, coined as artificial capillaries, exhibit excellent barrier function with reproducible control over lumen sizes ({phi}=8-35{micro}m) and their architectures (straight, curvatures, tapered, branched). The physical flow parameters measured across the lumen (namely, flow shear) and at the channel outlets (flow velocities) have been validated against high-fidelity numerical assessments from the Large Eddy Simulation scheme within the digitized versions of the microchannels. The experiment-computation compatibility enabled us to predict changes in regional velocity and wall shear stresses within artificial capillaries, for various capillary architectures. We also show that in situ editing of artificial capillaries in the form of adding new branches or adding occlusions is possible. Lastly, we developed a co-culture model which enables the study of stromal cells with artificial capillaries using conventional imaging methods. We envision that acellular chips with two seeding ports can be readily shipped worldwide and could potentially be adopted as a new technology to study microvascular biology in a reproducible manner.
Burr, D. J.; Nitsche, R.; Ravaro, E.; Wipf, S.; Ganga, P. L.; Balsamo, M.; Pellari, S. S.; Caltavituro, F.; Gisi, M.; de Almeida, R. C.; Manieri, P.; Sgambati, A.; Moratto, C.; Nürnberg, D. J.; Kish, A.; Elsaesser, A.
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Space-based platforms currently represent the most accurate means to experimentally assess the influence of the space environment on biological systems. However, performing such experiments remains technically challenging and requires highly specialized instrumentation. This study describes the current development and hardware qualification of ExocubeBio, a miniaturized experimental platform for in-situ biological space exposure. This experiment is scheduled for installation on the exterior of the International Space Station in 2027, as part of Exobio, the European Space Agencys new generation exobiology exposure facility. ExocubeBio will expose live microbial samples to the low Earth orbit environment, and combine autonomous in-situ optical density and fluorescence measurements, with the capacity to return preserved samples to Earth. Achieving these experimental goals requires a specialized, robust and reliable hardware system. The ExocubeBio hardware testing described here includes assessment of material biocompatibility and durability, functional validation of the miniaturized fluidic system, and optimization of the integrated optical subsystem for optical density and fluorescence measurements. These results demonstrate that the ExocubeBio experimental hardware components can each execute their core functional and operational requirements; subsystems allow for sample exposure, in-situ measurements of microbial cultures, and the chemical preservation of samples for post-flight analysis. As ExocubeBio transitions from hardware development to mission readiness, the results presented here validate the overall design and engineering approaches utilized. By combining the strengths of in-situ monitoring and sample return, ExocubeBio represents a significant advancement in space-based experimentation, and will provide new insights into microbial responses to the space environment.
Sadanandan, B.; Sunder, S.; Vijayalakshmi, V.; Ashrit, P.; Marabanahalli Yogendraiah, K.; Shetty, K.
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A compact, in-house developed ultraviolet germicidal irradiation (UVGI) system adaptable to static, mobile, or robotic platforms was developed for the effective sterilization of bacteria and fungi using a wireless mode of operation. Under controlled laboratory conditions, its efficacy was evaluated against three representative biofilm-forming pathogens: Bacillus subtilis (Gram-positive, spore-forming, motile bacterium), Escherichia coli K12 (Gram-negative, non-spore-forming, non-motile bacterium), and Candida albicans M-207 (multi-drug-resistant, clinical yeast isolate). Microbial viability following UVGI exposure was assessed using colony-forming unit (CFU) and MTT assays, and morphological alterations were characterized by scanning electron microscopy (SEM). Cultures were exposed to UV-C radiation at distances of 1-5 m for 15-90 min. CFU assay demonstrated 100% kill of all tested organisms at 1 m and 15 min, corresponding to doses of 600.3, 576 & 697.5 mJ/cm{superscript 2}. Although MTT assays indicated residual metabolic activity under the same conditions, CFU results confirmed that surviving cells were unable to proliferate, highlighting the robustness of UV treatment for long-term inactivation. SEM confirmed distinct morphological alterations such as complete destruction of extracellular matrix & reduction in number of cells indicating cell death with increase in UV dose as compared to controls. A dose & time-dependent inactivation of biofilm-forming bacteria & fungi was observed on exposure to UVGI. Therefore, this pilot study validates the effectiveness of the newly developed UVGI surface sterilizer against biofilm-forming bacterial and fungal pathogens. Overall, the system demonstrates proof-of-concept efficacy under laboratory conditions and holds strong potential for future development and validation in hospitals and other contaminated public spaces. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/715580v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@150cefcorg.highwire.dtl.DTLVardef@450831org.highwire.dtl.DTLVardef@1cfd6borg.highwire.dtl.DTLVardef@1419ba8_HPS_FORMAT_FIGEXP M_FIG C_FIG IMPORTANCEMicroorganisms that form biofilms on surfaces are difficult to eliminate and contribute to the spread of infections in healthcare and indoor environments. There is a need for practical, easy-to-use disinfection technologies that can effectively reduce such contamination. In this study, we developed a compact, in-house, wireless UV-C disinfection system designed for flexible operation across different surface types. The system was evaluated under controlled laboratory conditions using representative biofilm-forming bacterial and fungal pathogens. Our findings show that the system can effectively reduce microbial contamination, demonstrating proof-of-concept efficacy. This work highlights the potential of accessible, non-chemical UV-based technologies and supports their further validation for applications in real-world disinfection settings.
Shuaibu, I. I.; Khan, M. A.; Alkhamis, D.; Alkhamis, A.
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BackgroundSepsis-induced mortality is frequently driven by the systemic dissemination of pore-forming toxins (PFTs), such as Staphylococcus aureus alpha-hemolysin. Biomimetic "nanosponges" which are nanoparticles coated in red blood cell (RBC) membranes have emerged as a promising detoxification strategy. However, current methods rely largely on empirical iteration, often failing to optimize the competitive binding kinetics required to outcompete native RBCs in a high-flow hemodynamic environment. MethodsWe developed a deterministic ordinary differential equation (ODE) kinetic model based on the law of mass action to simulate the competitive inhibition of alpha-toxin by decoy nanoparticles. Unlike prior geometric models, this study explicitly tracked molar receptor concentrations to enforce saturation kinetics and mass conservation. We performed a multi-parametric sweep of nanoparticle radius (r_{NP}: 50-200 nm) and receptor surface density (d_{rec: 200-10,000 sites {micro}m{square}2) to identify the design window that maximizes toxin sequestration efficiency within a clinically relevant timeframe (60 minutes). ResultsBaseline simulations established a native RBC receptor concentration of 3.34 x 10^{-7} M. The optimization landscape revealed a non-linear dependence on receptor density rather than particle size. The optimal design window was identified at a receptor density of >8,000 sites {micro}m{square}2 on an 80 nm vector, achieving a theoretical toxin neutralization efficiency of 91.79%. Notably, complete (100%) neutralization was not observed even under optimized conditions, suggesting a theoretical upper bound imposed by physiological competition. In contrast, standard biomimetic formulations (low-density, 100 nm) achieved suboptimal capture, failing to prevent significant toxin-RBC interaction. ConclusionWe demonstrate that "decoy" efficacy is governed primarily by receptor surface density rather than geometric surface area. Our model suggests that current manufacturing protocols, which prioritize particle stability over receptor enrichment, may be kinetically insufficient for human application. These findings provide a rational design framework for next-generation nanotoxoid therapeutics.
Ballatore, F.; Madzvamuse, A.; Jebane, C.; Helfer, E.; Allena, R.
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Understanding how cells migrate through confined environments is crucial for elucidating fundamental biological processes, including cancer invasion, immune surveillance, and tissue morphogenesis. The nucleus, as the largest and stiffest cellular organelle, often limits cellular deformability, making it a key factor in migration through narrow pores or highly constrained spaces. In this work, we introduce a geometric surface partial differential equation (GS-PDE) model in which the cell plasma membrane and nuclear envelope are described as evolving energetic closed surfaces governed by force-balance equations. We replicate the results of a biophysical experiment, where a microfluidic device is used to impose compressive stresses on cells by driving them through narrow microchannels under a controlled pressure gradient. The model is validated by reproducing cell entry into the microchannels. A parametric sensitivity analysis highlights the dominant influence of specific parameters, whose accurate estimation is essential for faithfully capturing the experimental setup. We found that surface tension and confinement geometry emerge as key determinants of translocation efficiency. Although tailored to this specific setup for validation purposes, the framework is sufficiently general to be applied to a broad range of cell mechanics scenarios, providing a robust and flexible tool for investigating the interplay between cell mechanics and confinement. It also offers a solid foundation for future extensions integrating more complex biochemical processes such as active confined migration.
Bauer, J. E. S.; Alibhai, F. J.; Vatani, P.; Romero, D. A.; Laflamme, M. A.; Amon, C. H.
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PurposeLarge quantities of human pluripotent stem cells (hPSCs) are required for clinical applications. 3D suspension cultures are suitable for large scale manufacturing of hPSCs but yield, viability and quality are affected by the hydrodynamic environment. This paper characterizes the hydrodynamic environment inside vertical wheel bioreactors (VWBRs) as a function of size and agitation rates, measures its effect on cell aggregation and proliferation, and proposes the use of Lagrangian-based shear stress and energy dissipation rate (EDR) exposures to support scale-up. MethodsIn silico: Transient, 3D, turbulent flow simulations are conducted for two VWBR sizes (100, 500 mL) at five agitation rates between 20 and 80 rpm. Trajectories of cell aggregates of sizes from 200 to 1,000 microns are calculated, and shear stress and EDR exposures are collected along these trajectories. In vitro: ESI-017 hPSCs were cultured in VWBRs for 6 days. Aggregation efficiency and daily fold ratios were calculated based on cell counts and initial inoculation density. ResultsAggregate size, agitation rate and bioreactor size modulate cell aggregate exposures to EDR and shear stress, which significantly depart from maximum or volume average metrics used for scale-up. Combined in vitro/in silico results show EDR affects aggregation efficiency, cell counts and aggregate size, and has a small effect on daily fold ratios but a significant effect on total fold ratio. ConclusionHistory of trajectory-based cell aggregate exposures to EDRs provide a better scale-up basis for VWBRs than volume-averaged EDR. Shear stress does not significantly affect hPSC aggregation, proliferation and expansion in VWBRs under the tested conditions.
Qu, S.; Sillmann, J.; Barrett, B. W.; Graffy, P. M.; Poschlod, B.; Brunner, L.; Mansour, R.; Szombathely, M. v.; Hay-Chapman, F.; Horton, T. H.; Chan, J.; Rao, S. K.; Woods, K.; Kho, A. N.; Horton, D. E.
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As climate change intensifies, health risks from extreme heat are rising. Accurate assessment of heat vulnerability at high spatial resolution is crucial for developing effective adaptation strategies, particularly in socioeconomically heterogeneous urban settings. However, the identification of key indicators underlying heat vulnerability remains challenging. Using Chicago, Illinois (USA) as a case study, we systematically compare different variable selection strategies in community-level heat vulnerability assessments. We take the conventional unsupervised principal component analysis (PCA)-based Heat Vulnerability Index (HVI) as a baseline, and compare it with supervised approaches that incorporate variable selection, including machine learning algorithms (Lasso regression, Random Forest, and XGBoost) as well as traditional statistical methods (simple linear regression and polynomial regression). Using the vulnerability indicator subsets identified by each variable selection method, we construct multiple HVIs and evaluate their performance against heat-related excess mortality. Our work indicates that supervised variable selection improves the performance of HVIs in capturing heat-related health risks. Among all methods, the Random Forest-based variable selection algorithm achieves the best overall results, highlighting the potential of machine learning to enhance heat vulnerability assessment tools. Our results demonstrate that poverty rate, lack of air conditioning, and proportion of residents aged 65 and above are robust determinants of heat vulnerability in Chicago.
Mizoguchi, S.; Lee, V.; Kim, H.; Edelstein, S. E.; Wang, N.; Tomas Gracia, M.; Danelski, C.; Haynes, C.; Rivero, R.; Stitelman, D.; Obata, T.; Greaney, A. M.; Tsuchiya, T.; Kyriakides, T.; Kaminski, N.; Raredon, M. S. B.
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Recent research has emphasized the critical role of cell state transitions in tissue homeostasis. In lung biology, transitional cells are recognized as a feature of tissue-scale processes during both normal physiology and disease. The precise way that transitional cell states emerge and are regulated remains to be determined. Engineered tissues, built in a laboratory through bioengineering approaches, allow detailed study of cellular states that are not commonly found in native biology, and allow opportunities to directly induce and manipulate cellular transitions. The following study explores and characterizes epithelial cell states that emerge via cellular reprogramming in a tissue engineering context. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/701406v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1d456f3org.highwire.dtl.DTLVardef@1989ba5org.highwire.dtl.DTLVardef@127dd7org.highwire.dtl.DTLVardef@3dd7a_HPS_FORMAT_FIGEXP M_FIG C_FIG
Tang, Y.; Oon, W. Y.; Lee, W.-N.
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The acoustoelectric (AE) effect, in which acoustic waves modulate the electrical properties of a conductive medium, holds significant potential for biomedical imaging. While classic models describe the phenomenon through conductivity modulation, a detailed understanding of its microscopic origins, particularly the role of ion behaviours, remains lacking. This study introduces a novel electrokinetic perspective by investigating how ultrasound modulates ion-solvent interactions, thereby bridging macroscopic AE signals with underlying ion dynamics. Through finite element simulations of a dilute NaCl solution, we demonstrate that acoustic pressure waves induce local variations in ion mobility and diffusion by altering ion hydration shells and solvent viscosity. These changes disrupt the balance among Coulombic, diffusive, and frictional forces on individual ions, leading to the local conductivity modulation. Furthermore, simulations reveal that acoustic perturbation of the electrode-electrolyte interface (EEI) significantly enhances AE signal generation, highlighting the EEIs critical role in AE-related applications. By linking acoustic modulation to fundamental ion-solvent interactions, this work not only provides a foundation for more accurate, microscopically grounded models of the AE effect but also connects AE effect modelling to the active research of solvation dynamics in physical chemistry.
Mitra, H.; Nakate, P.; Stevenson, M. J.; Ardekani, A. M.
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Efficient drug delivery using nanoparticles (NPs) critically depends on their ability to diffuse through biological tissues to reach target cells at therapeutic concentrations. The extracellular matrix (ECM) poses a key barrier to such transport, which directly influences bio-distribution, cellular uptake, and overall therapeutic efficacy. A key regulator of this transport is hyaluronic acid/hyaluronan (HA), a major ECM polysaccharide that forms a hydrated, viscoelastic network. Increased/reduced hyaluronan concentration can elevate/decrease ECM bulk and effective viscosity. Increase in effective viscosity at the nanometer/micrometer length scales can hinder NP mobility through steric obstruction and hydrodynamic drag. There is a large variability in the HA molecular weights and concentrations, especially across age, tissue/organ, and pathological conditions. This work aims to study the diffusion of different NP types in the mixtures of HA polymers with variable molecular weights using the dynamic light scattering technique (DLS). Furthermore, we perform coarse-grained molecular dynamics (CG-MD) simulations for a model system to complement our findings from the dynamic light scattering experiments. We observe NP undergo anomalous diffusion, which is strongly dependent on the ratio of particle size/HA network mesh size, especially for higher molecular weight mixtures. This is strongly influenced by the effective viscosity, which is defined at the local environment experienced by the NPs. Our work highlights developing a simplified predictive framework coupled with simulations for a target-specific extracellular matrix environment.
WANG, K.; Sun, X.; Lin, K.; Chen, X.; Wang, Q.
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Microbially induced concrete corrosion (MICC) is a significant issue that reduces the service life of sewer systems. Bacteriostatic agent in concrete can inhibit microbial activity and the process of MICC to some extent. However, a systematic comparison of the inhibition effects of various bacteriostatic agents on MICC remains lacking. In this study, three bacteriostatic agents (copper oxide, nickel, and sodium tungstate) were investigated for their inhibitory effects on MICC. For each inhibitor, the cement mortar coupons with 0.05 wt%, 0.1 wt%, and 0.2 wt% of the inhibitor were prepared. The coupons were partially submerged in sewage of a controlled laboratory corrosion chamber (20 {+/-} 5 ppm H2S) to simulate the tidal region of gravity sewer. During the 56 days of exposure, the intensification of pores, cracks, surface erosion, and spalling was observed on all coupons. After 56 days of exposure, the sulfate concentration and adenosine triphosphate (ATP) content of coupons without inhibitor were 10.65 mg/cm2 and 30.17 {+/-} 3.87 mol/cm2, respectively. They were higher than those of coupons containing 0.05 wt%, 0.1 wt%, and 0.2 wt% of copper oxide and 0.05wt% of nickel. The temporal profiles of ATP of coupons without inhibitor was similar to those of coupons containing sodium tungstate. After exposure for 28 days, the surface pH of coupons without inhibitor was 7.45, meanwhile of those coupons containing 0.2 wt% of copper oxide and 0.05 wt% of nickel were 9.42 and 9.93, respectively. Those results indicated that the bacteriostatic effect of copper oxide and nickel (0.05 wt %) was found to be the most prominent. The findings indicate that a single bacteriostatic agent is only effective during specific corrosion stages, suggesting that a combination of multiple agents may be a promising strategy to combat the multi-stage MICC process over the long term. This study provides a theoretical basis for the selection and development of protective materials against concrete corrosion in sewer networks.
Saum, K. L.; Campos, B.; Celdran-Bonafonte, D.; Oren, L.; Owens, A. P.; Roy-Chaudhury, P.
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The arteriovenous fistula (AVF) is the preferred method of vascular access for hemodialysis; however, 30-50% of AVFs undergo primary failure and are unsuitable for clinical use. As disturbed hemodynamics initiate endothelial injury and intimal hyperplasia, we designed an endovascular flow-conditioning anastomotic device (FCAD) to directly improve AVF hemodynamics and protect the anastomotic region. Using computational fluid dynamics, we characterized the flow field and wall shear stress (WSS) profiles in idealized AVF models with and without the FCAD. Incorporation of the FCAD into a brachiocephalic AVF model reduced regions of oscillatory WSS and generated a symmetrical flow profile in the draining vein compared to a reference AVF. Parametric studies also identified an FCAD geometry with a tab angle, height, and aspect ratio of 30{degrees}, 0.1 diameters, and 1.0 restored time-averaged WSS along the inner venous wall, achieving a physiological level without inducing regions of oscillatory flow throughout the cardiac cycle. Similar findings were observed with an in vitro model using particle imaging velocimetry. This study demonstrates the feasibility of the FCAD to normalize venous flow and WSS while imposing minimal resistance to blood flow. Restoring physiological WSS levels on the venous wall is expected to preserve endothelial function and improve AVF maturation.
Arumugam, D.; Ghosh, M.
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BackgroundTo control leishmaniasis, chemotherapy drugs are currently under development. However, these drugs often exhibit poor efficacy and are associated with toxicity, adverse effects, and drug resistance. At present, no specific drug is available for the treatment of leishmaniasis. Meanwhile, vaccine research is ongoing. Recent studies have analysed some experimental vaccines using mathematical models. AimIn previous work, drug targeting was focused on the entire human body rather than specifically addressing infected macrophages and parasites. In our current approach, we aim to eliminate infected macrophages and parasites through nano-drug design. Specifically, we utilise two types of nanoparticles: iron oxide and citric acid-coated iron oxide. Moving forward, we plan to advance this strategy using mathematical modelling of macrophage-parasite interactions. MethodsWe design PDE-based models of macrophages and parasites, incorporating cytokine dynamics, to support nano-drug development. Drug efficacy is estimated using posterior distributions to analyse phenotypic fluctuations of macrophages and parasites during the design phase. We investigate implicit and semi-implicit treatment schemes, focusing on energy decay properties. To model drug flow during treatment, we introduce a three-phase moving boundary problem. Comparative analyses are conducted to evaluate macrophage and parasite behaviour with and without treatment. Finally, the entire framework is implemented within a virtual lab environment. ResultsThe results show that the nano-drug exhibits better efficacy compared to combined drug doses. We analysed and compared two types of nano-drug particles: iron oxide and citric acid-coated iron oxide. We discuss how the drug effectively targets and eliminates infected macrophages and parasites. ConclusionOur models results and simulations will support researchers conducting further studies in nano-drug design for leishmaniasis. These simulations are performed within a virtual lab environment.
Stewart, M.; Pradhan, H.; Zhuang, X.; Wang, Y.
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Silver (Ag+) ions are known to be toxic to bacteria, cells, organisms and living systems; yet its impacts on the locomotion of surface-crawling organisms remain poorly quantified. Here we investigated the short-term (0-6 hours) effects of Ag+ ions on the locomotion of Drosophila melanogaster larvae on flat agarose surfaces containing Ag+ ions at different concentrations (0, 1, 10, and 100 mM). By quantifying their locomotion, we found that Drosophila larvae showed shorter accumulated distances and reduced crawling speed. Additionally, we quantified the go/stop dynamics and peristalsis of the larvae and observed that Ag+ ions disrupted the normal, rhythmic, peristaltic contraction of the larvae and "trapped" them in the stop phase. Such toxic effects were dependent on Ag+ concentration and exposure duration.