The lysogenic filamentous bacteriophage phage Pf slows mucociliary transport.

is a major pulmonary pathogen causing chronic pulmonary infections in people with cystic fibrosis (CF). The and lysogenic bacteriophage, Pf phage, is abundant in the airways of many people with CF and has been associated with poor outcomes in a cross-sectional cohort study. Previous studies have identified roles for Pf phage in biofilm formation, specifically forming higher-order birefringent, liquid crystals when in contact with other biopolymers in biofilms.

Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding.

Despite great progress in the field, chronic () infections remain a major cause of morbidity and mortality in patients with cystic fibrosis, necessitating treatment with inhaled antibiotics. Pf phage is a filamentous bacteriophage produced by that has been reported to act as a structural element in biofilms. Pf presence has been associated with resistance to antibiotics and poor outcomes in cystic fibrosis, though the underlying mechanisms are unclear.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Biochemical, biophysical, and immunological characterization of respiratory secretions in severe SARS-CoV-2 infections.

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e.

Biochemical, Biophysical, and Immunological Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections.

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e.

Filamentous Bacteriophages and the Competitive Interaction between Pseudomonas aeruginosa Strains under Antibiotic Treatment: a Modeling Study.

Pseudomonas aeruginosa () is a major bacterial pathogen responsible for chronic lung infections in cystic fibrosis patients. Recent work has implicated Pf bacteriophages, nonlytic filamentous viruses produced by , in the chronicity and severity of infections. Pf phages act as structural elements in biofilms and sequester aerosolized antibiotics, thereby contributing to antibiotic tolerance.

Dynamic light scattering microrheology for soft and living materials.

We present a method for using dynamic light scattering in the single-scattering limit to measure the viscoelastic moduli of soft materials. This microrheology technique only requires a small sample volume of 12 μL to measure up to six decades in time of rheological behavior. We demonstrate the use of dynamic light scattering microrheology (DLSμR) on a variety of soft materials, including dilute polymer solutions, covalently-crosslinked polymer gels, and active, biological fluids.

Weekly injection of IL-2 using an injectable hydrogel reduces autoimmune diabetes incidence in NOD mice.

Aims/hypothesis: IL-2 injections are a promising therapy for autoimmune type 1 diabetes but the short half-life of this cytokine in vivo limits effective tissue exposure and necessitates frequent injections. Here we have investigated whether an injectable hydrogel could be used to promote prolonged IL-2 release in vivo.

Methods: Capitalising on the IL-2-binding capabilities of heparin, an injectable hydrogel incorporating clinical-grade heparin, collagen and hyaluronan polymers was used to deliver IL-2.

Biochemical and Biophysical Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections.

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e.

Evidence of a preferred kinetic pathway in the carnitine acetyltransferase reaction.

Mammalian carnitine acetyltransferase (CrAT) is a mitochondrial enzyme that catalyzes the reversible transfer of an acetyl group from acetyl-CoA to carnitine. CrAT knockout studies have shown that this enzyme is critical to sustain metabolic flexibility, or the ability to switch between different fuel types, an underlying theme of the metabolic syndrome. These recent physiological findings imply that CrAT dysfunction, or its catalytic impairment, may lead to disease.

Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy.

Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties.

Engineered materials for organoid systems.

Organoids are 3D cell culture systems that mimic some of the structural and functional characteristics of an organ. Organoid cultures provide the opportunity to study organ-level biology in models that mimic human physiology more closely than 2D cell culture systems or non-primate animal models. Many organoid cultures rely on decellularized extracellular matrices as scaffolds, which are often poorly chemically defined and allow only limited tunability and reproducibility.

Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening progressive lung disorder with limited therapeutic options. While interleukin-10 (IL-10) is a potent anti-inflammatory and anti-fibrotic cytokine, its utility in treating lung fibrosis has been limited by its short half-life. We describe an innovative hydrogel-based approach to deliver recombinant IL-10 to the lung for the prevention and reversal of pulmonary fibrosis in a mouse model of bleomycin-induced lung injury.

Review: Bioengineering strategies to probe T cell mechanobiology.

T cells play a major role in adaptive immune response, and T cell dysfunction can lead to the progression of several diseases that are often associated with changes in the mechanical properties of tissues. However, the concept that mechanical forces play a vital role in T cell activation and signaling is relatively new. The endogenous T cell microenvironment is highly complex and dynamic, involving multiple, simultaneous cell-cell and cell-matrix interactions.

Hyaluronan content governs tissue stiffness in pancreatic islet inflammation.

We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.

Amine-Reactive Azlactone-Containing Nanofibers for the Immobilization and Patterning of New Functionality on Nanofiber-Based Scaffolds.

We report the design of amine-reactive polymer nanofibers and nonwoven reactive nanofiber mats fabricated by the electrospinning of azlactone-functionalized polymers. We demonstrate that randomly oriented nanofibers fabricated using a random copolymer of methyl methacrylate and 2-vinyl-4,4-dimethylazlactone contain intact and reactive azlactone groups that can be used to introduce new chemical functionality and modulate important interfacial properties of these materials (e.g.

Nonwoven Polymer Nanofiber Coatings That Inhibit Quorum Sensing in Staphylococcus aureus: Toward New Nonbactericidal Approaches to Infection Control.

We report the fabrication and biological evaluation of nonwoven polymer nanofiber coatings that inhibit quorum sensing (QS) and virulence in the human pathogen Staphylococcus aureus. Our results demonstrate that macrocyclic peptide 1, a potent and synthetic nonbactericidal quorum sensing inhibitor (QSI) in S. aureus, can be loaded into degradable polymer nanofibers by electrospinning and that this approach can deposit QSI-loaded nanofiber coatings onto model nonwoven mesh substrates.

Slippery Liquid-Infused Porous Surfaces that Prevent Bacterial Surface Fouling and Inhibit Virulence Phenotypes in Surrounding Planktonic Cells.

Surfaces that can both prevent bacterial biofouling and inhibit the expression of virulence phenotypes in surrounding planktonic bacteria are of interest in a broad range of contexts. Here, we report new slippery-liquid infused porous surfaces (SLIPS) that resist bacterial colonization (owing to inherent "slippery" surface character) and also attenuate virulence phenotypes in non-adherent cells by gradually releasing small-molecule quorum sensing inhibitors (QSIs). QSIs active against Pseudomonas aeruginosa can be loaded into SLIPS without loss of their slippery and antifouling properties, and imbedded agents can be released into surrounding media over hours to days depending on the structures of the loaded agent.

Nanoporous Superhydrophobic Coatings that Promote the Extended Release of Water-Labile Quorum Sensing Inhibitors and Enable Long-Term Modulation of Quorum Sensing in .

Materials and coatings that inhibit bacterial colonization are of interest in a broad range of biomedical, environmental, and industrial applications. In view of the rapid increase in bacterial resistance to conventional antibiotics, the development of new strategies that target nonessential pathways in bacterial pathogens-and that thereby limit growth and reduce virulence through nonbiocidal means-has attracted considerable attention. Bacterial quorum sensing (QS) represents one such target, and is intimately connected to virulence in many human pathogens.

Superhydrophobic polymer multilayers that promote the extended, long-term release of embedded water-soluble agents.

Polymer multilayers that exhibit surface and bulk superhydrophobicity are demonstrated to promote long-term release of water-soluble agents (for ca.1 year) when submerged in water. The extremely nonwetting nature of these materials prevents rapid influx of water, addressing a key limitation inherent to polyelectrolytebased multilayers that release imbedded agents quickly.

Surface coatings that promote rapid release of peptide-based AgrC inhibitors for attenuation of quorum sensing in Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen responsible for a variety of life-threatening infections. The pathogenicity of this organism is attributed to its ability to produce a range of virulence factors and toxins, including the superantigen toxic shock syndrome toxin-1 (TSST-1). While many S.

Good species behaving badly: Non-monophyly of black fly sibling species in the Simulium arcticum complex (Diptera: Simuliidae).

Mitochondrial based phylogenetic reconstructions often show deviations from species-level monophyly. We used the Simulium arcticum species complex (Diptera: Simuliidae) as a model system for interpreting non-monophyly in light of chromosomal data supporting species status of siblings. For cytogenetic identification of morphologically indistinguishable black fly sibling species, larvae must be preserved in Carnoy's solution, a fixative known to degrade DNA.