43 research outputs found
Supported planar bilayer formation by vesicle fusion: the interaction of phospholipid vesicles with surfaces and the effect of gramicidin on bilayer properties using atomic force microscopy
AbstractWe have used magnetic alternating current mode atomic force microscopy (MAC–AFM) to investigate the formation of supported phospholipid bilayers (SPB) by the method of vesicle fusion. The systems studied were dioleoylphosphatidylcholine (DOPC) on mica and mica modified with 3-aminopropyl-triethoxy-silane (APTES), and DOPC vesicles with gramicidin incorporated on mica and APTES-modified mica. The AFM images reveal three stages of bilayer formation: localized disklike features that are single bilayer footprints of the vesicles, partial continuous coverage, and finally complete bilayer formation. The mechanism of supported phospholipid bilayers formation is the fusion of proximal vesicles, rather than surface disk migration. This mechanism does not appear to be affected by incorporation of gramicidin or by surface modification. Once formed, the bilayer develops circular defects one bilayer deep. These defects grow in size and number until a dynamic equilibrium is reached
Monitoring inflammation and airway remodeling by fluorescence molecular tomography in a chronic asthma model
Background: Asthma is a multifactorial disease for which a variety of mouse models have been developed. A major drawback of these models is represented by the transient nature of the airway pathology peaking 24-72h after challenge and resolving in 1-2weeks. We characterized the temporal evolution of pulmonary inflammation and tissue remodeling in a recently described mouse model of chronic asthma (8week treatment with 3 allergens: Dust mite, Ragweed, and Aspergillus; DRA). Methods: We studied the DRA model taking advantage of fluorescence molecular tomography (FMT) imaging using near-infrared probes to non-invasively evaluate lung inflammation and airway remodeling. At 4, 6, 8 or 11weeks, cathepsin- and metalloproteinase-dependent fluorescence was evaluated in vivo. A subgroup of animals, after 4weeks of DRA, was treated with Budesonide (100\u3bcg/kg intranasally) daily for 4weeks. Results: Cathepsin-dependent fluorescence in DRA-sensitized mice resulted significantly increased at 6 and 8weeks, and was markedly inhibited by budesonide. This fluorescent signal well correlated with ex vivo analysis such as bronchoalveolar lavage eosinophils and pulmonary inflammatory cell infiltration. Metalloproteinase-dependent fluorescence was significantly increased at 8 and 11weeks, nicely correlated with collagen deposition, as evaluated histologically by Masson's Trichrome staining, and airway epithelium hypertrophy, and was only partly inhibited by budesonide. Conclusions: FMT proved suitable for longitudinal studies to evaluate asthma progression, showing that cathepsin activity could be used to monitor inflammatory cell infiltration while metalloproteinase activity parallels airway remodeling, allowing the determination of steroid treatment efficacy in a chronic asthma model in mice
Azithromycin inhibits nuclear factor-κB activation during lung inflammation : an in vivo imaging study
We studied in vivo the potential involvement of nuclear factor-\u3baB (NF-\u3baB) pathway in the molecular mechanism of the anti-inflammatory and immunomodulatory activity of azithromycin in the lung. Mice transiently transfected with the luciferase gene under the control of a NF-\u3baB responsive element were used to assess in vivo NF-\u3baB activation by bioluminescence imaging. Bioluminescence as well as inflammatory cells and concentrations of proinflammatory cytokines in bronchoalveolar lavage fluids, were monitored in an acute model of pulmonary inflammation resulting from intratracheal instillation of lipopolysaccharide. Lipopolysaccharide (LPS) instillation induced a marked increase in lung bioluminescence in mice transiently transfected with the luciferase gene under the control of an NF-\u3baB responsive element, with significant luciferase expression in resident cells such as endothelial and epithelial cells, as assessed by duoplex immunofluorescence staining. Activation of NF-\u3baB and inflammatory cell lung infiltration linearly correlated when different doses of bortezomib were used to inhibit NF-\u3baB activation. Pretreatment with azithromycin significantly decreased lung bioluminescence and airways cell infiltration induced by LPS, also reducing proinflammatory cytokines concentrations in bronchoalveolar lavages and inhibiting NF-\u3baB nuclear translocation. The results obtained using a novel approach to monitor NF-\u3baB activation, provided, for the first time, in vivo evidence that azithromycin treatment results in pulmonary anti-inflammatory activity associated with the inhibition of NF-\u3baB activation in the lung
Monitoring inflammation and airway remodeling by fluorescence molecular tomography in a chronic asthma model
Effects of non-local scattering on the aerodynamic coefficients of nano-particles
Most gas-surface interaction models used in rarefied gas dynamics assume that the space and time scale associated with gas-solid interaction are negligibly small. Accordingly, it is assumed that a gas molecule hitting a solid surface is instantaneously re-emitted at the same spatial location. However, as shown by molecular dynamics simulation, the re-emission event usually takes place at a distance of several molecular diameters from the first collision location. It is to expected that diffusion processes on the surface do affect the aerodynamic forces on particles transported by
a carrier gas, when the particle size is comparable with the distance covered by a molecule on the
solid surface during interaction. In such case, local gas-surface interaction models fail to predict the
correct drag on the particle. In this paper a non-local kinetic gas-surface interaction model is applied
to compute aerodynamic forces on spherical particles in the free molecular flow regime. Is is shown
that effective accommodation coefficients of nanosized particles depend on particle radius