Measuring the Interactions and Influence of Amphipathic Copolymers with Lipid Monolayers and Bilayers as Models of Biological Membranes

Amphipathic copolymers are useful materials for nanomedicine, owing to their ability to self-assemble into nanoparticles, act as surfactants for inorganic materials, or for their favorable interactions with lipid membranes. Despite their widespread use, there is still a range of questions about the physicochemical properties that are necessary to drive their interactions at biological interfaces. To fully understand these interactions requires a diverse range of complementary analytical techniques. In this work, a library of neutral amphipathic methacrylate copolymers is synthesized by reversible addition-fragmentation chain-transfer polymerization (RAFT) polymerization, to investigate the effect of polymer composition and nature of the hydrophobic comonomer on interactions with model lipid membranes. These materials are shown to interact with Langmuir lipid monolayers, and neutron reflectometry demonstrates that hydrophobic interactions lead to the polymers intercalating with the monolayers. More complex models of lipid bilayers are studied using an in situ quartz crystal microbalance (QCM) model and shows while the composition and hydrophobic comonomer affect the stability of these interactions, there is no effect on the viscoelasticity of the lipid membranes. The in-depth understanding of these interfacial interactions afforded by this suite of analytical tools will allow for more complex copolymers to be studied, providing a greater understanding of key processes in nanomedicine, such as cellular entry and endosomal escape.</p

Dependence of organic interlayer diffusion on glass-transition temperature in OLEDs

Organic light-emitting diodes (OLEDs) are subject to thermal stress from Joule heating and the external environment. In this work, neutron reflectometry (NR) was used to probe the effect of heat on the morphology of thin three-layer organic films comprising materials typically found in OLEDs. It was found that layers within the films began to mix when heated to approximately 20 °C above the glass-transition temperature (T) of the material with the lowest T. Diffusion occurred when the material with the lowest T formed a supercooled liquid, with the rates of interdiffusion of the materials depending on the relative T's. If the supercooled liquid formed at a temperature significantly lower than the T of the higher-T material in the adjacent layer, then pseudo-Fickian diffusion occurred. If the two T's were similar, then the two materials can interdiffuse at similar rates. The type and extent of diffusion observed can provide insight into and a partial explanation for the "burn in" often observed for OLEDs. Photoluminescence measurements performed simultaneously with the NR measurements showed that interdiffusion of the materials from the different layers had a strong effect on the emission of the film, with quenching generally observed. These results emphasize the importance of using thermally stable materials in OLED devices to avoid film morphology changes

Cephalosporin-3\u27-diazeniumdiolates:Targeted NO-donor prodrugs for dispersing bacterial biofilms

Biofilms are sessile communities of microbial cells contained within a self-produced exopolymeric matrix. Bacteria encased in biofilms exhibit upwards of 10–1000-fold higher resistance to biocides and traditional antibiotics than their planktonic counterparts (i.e. floating, unattached), and they are less susceptible to host immune defenses.[1, 2] Accordingly, chronic antimicrobial-tolerant bacterial infections are often biofilmbased (e.g. infections on indwelling medical devices and incurable Pseudomonas aeruginosa respiratory infections in cystic fibrosis (CF) sufferers).[3] Currently there are few effective therapeutics for clearing biofilm-based infections, and a critical need exists for new agents and treatment strategie

Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenza biofilm formation

Nontypeable Haemophilus influenzae (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesized that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonization and biofilm evelopment. We used a primary epithelial cell co-culture model to investigate NTHi infection. Primary airway epithelial cells from PCD and non-PCD patients were differentiated to ciliation using air-liquid interface culture and then co-cultured with NTHi. NTHi adherence was greater on PCD epithelial cells compared to non-PCD cells (P&lt;0.05) and the distribution of NTHi on PCD epithelium showed more aggregated NTHi in biofilms (P&lt;0.001). Apart from defective ciliary motility, PCD cells did not significantly differ from non-PCD epithelial cells in the degree of ciliation and epithelial integrity or in cytokine, LL-37 and NO production. Treatment of PCD epithelia using exogenous NO and antibiotic significantly reduced NTHi viability in biofilms compared to antibiotic treatment alone. Impaired ciliary function was the primary defect in PCD airway epithelium underlying susceptibility to NTHi biofilm development compared with non-PCD epithelium. Although NO responses were similar, use of targeted NO with antibiotics enhanced killing of NTHi in biofilms, suggesting a novel therapeutic approach

You're a useless person : The understanding of prostitution within a Cuban context of gender equality and machismo-leninismo

Nontypeable Haemophilus influenzae (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesized that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonization and biofilm evelopment. We used a primary epithelial cell co-culture model to investigate NTHi infection. Primary airway epithelial cells from PCD and non-PCD patients were differentiated to ciliation using air-liquid interface culture and then co-cultured with NTHi. NTHi adherence was greater on PCD epithelial cells compared to non-PCD cells (P&lt;0.05) and the distribution of NTHi on PCD epithelium showed more aggregated NTHi in biofilms (P&lt;0.001). Apart from defective ciliary motility, PCD cells did not significantly differ from non-PCD epithelial cells in the degree of ciliation and epithelial integrity or in cytokine, LL-37 and NO production. Treatment of PCD epithelia using exogenous NO and antibiotic significantly reduced NTHi viability in biofilms compared to antibiotic treatment alone. Impaired ciliary function was the primary defect in PCD airway epithelium underlying susceptibility to NTHi biofilm development compared with non-PCD epithelium. Although NO responses were similar, use of targeted NO with antibiotics enhanced killing of NTHi in biofilms, suggesting a novel therapeutic approach