Publications by authors named "Norman J Wagner"

Hydrogen-deuterium exchange (HDX) measured by small-angle neutron scattering (HDX-SANS) is used to measure HDX in bovine serum albumin (BSA) under different temperatures and formulation conditions. HDX-SANS measurements are performed at 40, 50, and 60 °C in DO after storing proteins at 4 °C for 1 week to pre-exchange the readily accessible hydrogens. This enables us to probe the long-time HDX of protons at the core of the BSA proteins, which is more challenging for solvent molecules to access.

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Electron transport in complex fluids, biology, and soft matter is a valuable characteristic in processes ranging from redox reactions to electrochemical energy storage. These processes often employ conductor-insulator composites in which electron transport properties are fundamentally linked to the microstructure and dynamics of the conductive phase. While microstructure and dynamics are well recognized as key determinants of the electrical properties, a unified description of their effect has yet to be determined, especially under flowing conditions.

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The Rouse dynamics of polymer chains in model nanocomposite polyethylene oxide/silica nanoparticles (NPs) was investigated using quasielastic neutron scattering. The apparent Rouse rate of the polymer chains decreases as the particle loading increases. However, there is no evidence of an immobile segment population on the probed time scale of tens of ps.

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Colloidal suspensions of anisotropic particles are ubiquitous in particle-based industries. Consequently, there is a need to quantify the effects of particle shape on equilibrium phases and kinetic state transitions, particularly at lower aspect ratios (L/D ≈ 1-10). We present a new, colloidal system comprised of hollow, octadecyl-coated silica rods with 40 nm diameter with controlled aspect ratio and thermoreversible short-range attractions.

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Acylated peptides composed of glucagon-like peptide-1 receptor agonists modified with a fatty acid side chain are an important class of therapeutics for type 2 diabetes and obesity but are susceptible to an unusual physical instability in the presence of hydrophobic surfaces, i.e., spontaneous emulsification, also known as ouzo formation in practice.

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Proteins are exposed to hydrostatic pressure (HP) in a variety of ecosystems as well as in processing steps such as freeze-thaw, cell disruption, sterilization, and homogenization, yet pressure effects on protein-protein interactions (PPIs) remain underexplored. With the goal of contributing toward the expanded use of HP as a fundamental control parameter in protein research, processing, and engineering, small-angle X-ray scattering was used to examine the effects of HP and ionic strength on ovalbumin, a model protein. Based on an extensive data set, we develop an empirical method for scaling PPIs to a master curve by combining HP and osmotic effects.

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Understanding protein dynamics and conformational stability holds great significance in biopharmaceutical research. Hydrogen-deuterium exchange (HDX) is a quantitative methodology used to examine these fundamental properties of proteins. HDX involves measuring the exchange of solvent-accessible hydrogens with deuterium, which yields valuable insights into conformational fluctuations and conformational stability.

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Monoclonal antibodies (mAbs) form viscoelastic gel-like layers at the air-water interface due to their amphiphilic nature, and this same protein characteristic can lead to undesired aggregation of proteins in therapeutic formulations. We hypothesize that the interfacial viscoelasticity and surface pressure of mAbs at the air-water interface will correlate with their long-term stability. To test this hypothesis, the interfacial viscoelastic rheology and surface pressure of five different antibodies with varying visible particle counts from a three-year stability study were measured.

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Understanding the interfacial structure-property relationship of complex fluid-fluid interfaces is increasingly important for guiding the formulation of systems with targeted interfacial properties, such as those found in multiphase complex fluids, biological systems, biopharmaceuticals formulations, and many consumer products. Mixed interfacial flow fields, typical of classical Langmuir trough experiments, introduce a complex interfacial flow history that complicates the study of interfacial properties of complex fluid interfaces. In this article, we describe the design, implementation, and validation of a new instrument capable of independent application of controlled interfacial dilation and shear kinematics on fluid interfaces.

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Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can induce aggregation and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution.

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We investigate the aging behavior in a well-studied model system comprised of a colloidal suspension of thermoreversible adhesive hard spheres (AHS) but thermally quenched below the gel transition to much larger depths than previously studied. The aging behavior in the model AHS system is monitored by small amplitude oscillatory shear rheology measurements conducted while rapidly quenching from the liquid state at 40 °C to a temperature below the gel temperature, and new, anomalous aging behaviors are observed. Shallow quenches lead to monotonic development of the elastic modulus with time, consistent with prior reports for the development of a homogeneous gel [Gordon et al.

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In this work, we outline the development of a thermodynamically consistent microscopic model for a suspension of aggregating particles under arbitrary, inertia-less deformation. As a proof-of-concept, we show how the combination of a simplified population-balance-based description of the aggregating particle microstructure along with the use of the single-generator bracket description of nonequilibrium thermodynamics, which leads naturally to the formulation of the model equations. Notable elements of the model are a lognormal distribution for the aggregate size population, a population balance-based model of the aggregation and breakup processes and a conformation tensor-based viscoelastic description of the elastic network of the particle aggregates.

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Article Synopsis
  • Research on shear thickening colloidal suspensions reveals that analyzing microstructures helps explain their unique flow properties while also testing existing theories and simulations related to various mechanisms.
  • Previous studies identified hydroclusters as a key feature of the shear thickened state, but questions about their mesoscale microstructure persisted.
  • This study uses neutron scattering to investigate the microstructure of these suspensions, finding that hydroclusters are localized, which aligns with some earlier findings but challenges recent simulations that suggested longer-range structures.
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Mask wearing and physical distancing are effective at preventing COVID-19 transmission. Little is known about the practice of these behaviors during physical activity (PA). In this longitudinal study, direct observation was used to describe COVID-19 prevention behaviors among physically active individuals.

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Polysorbate 80 (PS80), a nonionic surfactant used in pharmaceutical formulation, is known to be incompatible with -cresol, an antimicrobial agent for multi-dose injectable formulations. This incompatibility results in increased turbidity caused by micelle aggregation progressing over weeks or longer, where storage temperature, ionic strength, and component concentration influence the aggregation kinetics. Small-angle neutron scattering (SANS) analysis of PS80/-cresol solutions over a pharmaceutically relevant concentration range of each component reveals the cause of aggregation, the coalescence mechanism, and aggregate structure.

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Due to the potential impact on the diagnosis and treatment of various cardiovascular diseases, work on the rheology of blood has significantly expanded in the last decade, both experimentally and theoretically. Experimentally, blood has been confirmed to demonstrate a variety of non-Newtonian rheological characteristics, including pseudoplasticity, viscoelasticity, and thixotropy. New rheological experiments and the development of more controlled experimental protocols on more extensive, broadly physiologically characterized, human blood samples demonstrate the sensitivity of aspects of hemorheology to several physiological factors.

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Protein salting-out is a well established phenomenon that in many cases leads to amorphous structures and protein gels, which are usually not considered to be useful for protein structure determination. Here, microstructural measurements of several different salted-out protein dense phases are reported, including of lysozyme, ribonuclease A and an IgG1, showing that salted-out protein gels unexpectedly contain highly ordered protein nanostructures that assemble hierarchically to create the gel. The nanocrystalline domains are approximately 10-100 nm in size, are shown to have structures commensurate with those of bulk crystals and grow on time scales in the order of an hour to a day.

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An extensive data set has been developed and used to further the progress of a model-informed design of controlled drug release. An improved drug-release model with mechanistic modeling of hydrolytic polymer degradation is used and validated by comparing model predictions to in vitro experiments. Combining parameter estimates from the literature with model fits to the data set, this study can aid in achieving a priori design of controlled drug release from a model PLGA release system.

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The COVID-19 pandemic severely affected many aspects of human life. While most health agencies agree mask wearing and physical distancing reduce viral transmission, efforts to improve the assessment of these behaviors are lacking. This study aimed to develop a direct observation video method [Viral Transmission (VT)-Scan] for assessing COVID-19 transmission behaviors and related factors (e.

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Wrinkled polymer surfaces find broad applicability; however, the polymer substrates are often limited to poly(dimethylsiloxane) (PDMS), which limits spatial control over wrinkle features and surface chemistry. An approach to surface functionalization of wrinkled elastomer substrates is demonstrated through versatile, multistep thiol-ene click chemistry. The elastomer is formed using a thiol-Michael reaction of tetrathiol with excess diacrylates while wrinkle formation is induced through a second free radical UV polymerization of the acrylates on the surface of the elastomer.

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Recent advances in hemorheology are extended to study blood rheology across species, which has important clinical implications particularly in intravenous drug scaleup as drugs undergoing clinical trials are first tested in animals. Some of the first hemorheological measurements from seven different species under both steady and transient shear conditions are presented and modeled using a rheological model developed and validated on human blood rheology fit to 20 different donors. Despite similar physiological properties across the blood samples from different species, significant differences are observed, particularly at low shear rates.

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Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology.

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Aging in a model colloidal suspension comprised of particles with a thermoreversible attraction is studied using Rheo-SANS techniques in the attractive-driven glass state. Multiple thermal pathways lead to a common rheological and microstructural aging trajectory, as was observed previously for a thermoreversible gel. SANS measurements of the colloidal glass microstructure as a function of temperature and time during various quench protocols are quantitatively characterized in terms of an effective interaction strength that becomes an order parameter defining the microstructural state of the glass.

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The adsorption of monoclonal antibodies (mAbs) on hydrophobic surfaces is known to cause protein aggregation and degradation. Therefore, surfactants, such as Poloxamer 188, are widely used in therapeutic formulations to stabilize mAbs and protect mAbs from interacting with liquid-solid interfaces. Here, the adsorption of Poloxamer 188, one mAb and their competitive adsorption on a model hydrophobic siliconized surface is investigated with neutron scattering coupled with contrast variation to determine the molecular structure of adsorbed layers for each case.

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Hypothesis: Molecular engineering facilitates the development of a complex fluid with contradictory requirements of yield stress and sprayability, while minimizing the amount of structuring material (<0.05 wt%). This unique system can be achieved by a biopolymer hydrogel with tunable inter- and intra-molecular interactions for microstructural robustness and molecular extensibility by the variation of chemical conformations that microstructure breaks up under shear followed by a low molecularly extensible response.

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