Modeling the Microstructure and Stress in Dense Suspensions under Inhomogeneous Flow

Under inhomogeneous flow, dense suspensions exhibit complex behaviour that violates the conventional homogenous rheology. Specifically, one finds flowing regions with a macroscopic friction coefficient below the yielding criterion, and volume fraction above the jamming criterion. We demonstrate the underlying physics by incorporating shear rate fluctuations into a recently proposed tensor model for the microstructure and stress, and applying the model to an inhomogeneous flow problem. The model predictions agree qualitatively with particle-based simulations.Comment: 7 pages, 4 figure

Probing Membrane Viscosity and Interleaflet Friction of Supported Lipid Bilayers by Tracking Electrostatically Adsorbed, Nano-Sized Vesicles

Particle tracking is used to measure the diffusional motion of nanosized (≈100 nm), lipid vesicles that are electrostatically adsorbed onto a solid supported lipid bilayer. It is found that the motion of membrane-adhering vesicles is Brownian and depends inversely on the vesicle size, but is insensitive to the vesicle surface charge. The measured diffusivity agrees well with the Evans–Sackmann model for the diffusion of inclusions in supported, fluidic membranes. The agreement implies that the vesicle motion is coupled to that of a nanoscopic lipid cluster in the upper leaflet, which slides over the lower leaflet. The diffusivity of membrane-adhering vesicles is therefore predominantly governed by the interleaflet friction coefficient, while the diffusivity of single lipids is mainly governed by the membrane viscosity. Combined with fluorescence recovery after photobleaching analysis, the interleaflet friction coefficient and the membrane viscosity are determined by applying the Evans–Sackmann model to the measured diffusivity of membrane adhering vesicles and that of supported membrane lipids. This approach provides an alternative to existing methods for measuring the interleaflet friction coefficient and the membrane viscosity

Inhibition of granulocyte migration by tiotropium bromide

<p>Abstract</p> <p>Study objectives</p> <p>Neutrophil influx into the airways is an important mechanism in the pathophysiology of the inflammatory process in the airways of patients with chronic obstructive pulmonary disease (COPD). Previously it was shown that anticholinergic drugs reduce the release of non-neuronal paracrine mediators, which modulate inflammation in the airways. On this basis, we investigated the ability of the long-acting anticholinergic tiotropium bromide to inhibit a) alveolar macrophage (AM)-mediated chemotaxis of neutrophils, and b) cellular release of reactive oxygen species (ROS).</p> <p>Method</p> <p>AM and neutrophils were collected from 71 COPD patients. Nanomolar concentrations of tiotropium bromide were tested in AM cultured up to 20 h with LPS (1 μg/ml). AM supernatant was tested for TNFα, IL8, IL6, LTB4, GM-CSF, MIPα/β and ROS. It was further used in a 96-well chemotaxis chamber to stimulate the migration of fluorescence labelled neutrophils. Control stimulants consisted of acetylcholine (ACh), carbachol, muscarine or oxotremorine and in part PMA (phorbol myristate acetate, 0.1 μg/ml). Potential contribution of M_1-3-receptors was ascertained by a) analysis of mRNA transcription by RT-PCR, and b) co-incubation with selective M-receptor inhibitors.</p> <p>Results</p> <p>Supernatant from AM stimulated with LPS induced neutrophilic migration which could be reduced by tiotropium in a dose dependent manner: 22.1 ± 10.2 (3 nM), 26.5 ± 18,4 (30 nM), and 37.8 ± 24.0 (300 nM, p < 0.001 compared to non-LPS activated AM). Concomitantly TNFα release of stimulated AM dropped by 19.2 ± 7.2% of control (p = 0.001). Tiotropium bromide did not affect cellular IL8, IL6, LTB4, GM-CSF and MIPα/β release in this setting. Tiotropium (30 nM) reduced ROS release of LPS stimulated AM by 36.1 ± 15.2% (p = 0.002) and in carbachol stimulated AM by 46.2 ± 30.2 (p < 0.001). M3R gene expression dominated over M2R and M1R. Chemotaxis inhibitory effect of tiotropium bromide was mainly driven by M3R inhibition.</p> <p>Conclusion</p> <p>Our data confirm that inhibiting muscarinic cholinergic receptors with tiotropium bromide reduces TNFα mediated chemotactic properties and ROS release of human AM, and thus may contribute to lessen cellular inflammation.</p

Disentangling bulk polymers from adsorbed polymers using the quartz crystal microbalance

At sufficient adhesion energy, polymers may adsorb irreversibly at an interface, with many adhesion sites per polymer and significant changes in their conformation. In addition to irreversibly adsorbed polymers there may be reversibly adsorbed polymers, which are in dynamic equilibrium with bulk polymers, and which have fewer adhesion sites per polymer and less significant conformational changes. In this work, we simultaneously determine the viscoelasticity of irreversibly adsorbed polymers, reversibly adsorbed polymers, and bulk polymers. To this end, we combine hydrodynamic modelling with quartz crystal microbalance-dissipation (QCM-D) measurements involving an adsorbing target surface and a non-adsorbing, i.e., passivated surface. We apply the method to polyethylene glycol adsorption at the water–silica interface. The results demonstrate that the viscoelasticity of the reversibly adsorbed polymers is similar to that of the bulk polymers, whereas the irreversibly adsorbed polymers are less elastic. This is the first approach to decouple these viscoelastic contributions, which provides a new analytical tool to quantify the kinetics and conformation of reversibly adsorbed polymers, shedding light on polymer dynamics near interfaces

Fragile dense suspensions under shear rotation

While quasi-Newtonian complex fluids under steady-state flow, dense non-Brownian suspensions exhibit complex "macro-fragile" behaviors under unsteady flow conditions, as revealed by abrupt shear inversions (reversals). Here, we introduce an experimental setup to systematically explore their macro-fragile response to shear rotations, where one suddenly rotates the principal axes of shear by an angle $\theta$. This reveals a transient decrease of the shear stress under shear rotation. Moreover, the orthogonal shear stress, which vanishes in steady state, takes non-negligible values with a rich $\theta$-dependence, changing qualitatively with solid volume fraction $\phi$, and resulting in a force that tends to reduce or enhance the direction of flow for small or large $\phi$. These findings are confirmed and rationalized by particle-based numerical simulations and a recently proposed constitutive model. We show that the rotation angle dependence of the orthogonal stress results from from a $\phi$-dependent interplay between hydrodynamic and contact stresses.Comment: 5 pages + Supplementary Inf

Effect of Glucose on the Mobility of Membrane-Adhering Liposomes

Enclosed lipid bilayer structures, referred to as liposomes or lipid vesicles, have a wide range of biological functions, such as cellular signaling and membrane trafficking. The efficiency of cellular uptake of liposomes, a key step in many of these functions, is strongly dependent on the contact area between a liposome and a cell membrane, which is governed by the adhesion force w, the membrane bending energy κ, and the osmotic pressure Δp. Herein, we investigate the relationship between these forces and the physicochemical properties of the solvent, namely, the presence of glucose (a nonionic osmolyte). Using fluorescence microscopy, we measure the diffusivity D of small (∼50 nm radius), fluorescently labeled liposomes adhering to a supported lipid bilayer or to the freestanding membrane of a giant (∼10 μm radius) liposome. It is observed that glucose in solution reduces D on the supported membrane, while having negligible effect on D on the freestanding membrane. Using well-known hydrodynamic theory for the diffusivity of membrane inclusions, these observations suggest that glucose enhances the contact area between the small liposomes and the underlying membrane, while not affecting the viscosity of the underlying membrane. In addition, quartz crystal microbalance experiments showed no significant change in the hydrodynamic height of the adsorbed liposomes, upon adding glucose. This observation suggests that instead of osmotic deflation, glucose enhances the contact area via adhesion forces, presumably due to the depletion of the glucose molecules from the intermembrane hydration layer

A model derived from hydrodynamic simulations for extracting the size of spherical particles from the quartz crystal microbalance

One challenging aspect of quartz crystal microbalance (QCM) measurements is the characterization of adsorbed particles as the change in resonance frequency (Δf) is proportional not only to the inertia of the adsorbed layer but also to that of the hydrodynamically coupled fluid. Herein, by solving numerically the Navier–Stokes equations, we scrutinize Δf for sparsely deposited, rigid spherical particles that are firmly attached to an oscillating surface. The analysis is shown to be applicable to adsorbed, small unilamellar vesicles (SUVs) of controlled size under experimental conditions in which adhesion-induced vesicle deformation is negligible. The model supports a hydrodynamic explanation for the overtone dependence of Δf, and was fitted to experimental data concerning three monodisperse populations of SUVs with different average sizes ranging between 56 and 114 nm diameter. Using this procedure, we determined the average size of adsorbed vesicles to be within 16% of the size that was measured by dynamic light scattering experiments in bulk solution. In conclusion, this model offers a means to extract the particle size from QCM-D measurement data, with applications to biological and synthetic nanoparticles

Hydrodynamic Propulsion of Liposomes Electrostatically Attracted to a Lipid Membrane Reveals Size-Dependent Conformational Changes

The efficiency of lipid nanoparticle uptake across cellular membranes is strongly dependent on the very first interaction step. Detailed understanding of this step is in part hampered by the large heterogeneity in the physicochemical properties of lipid nanoparticles, such as liposomes, making conventional ensemble-averaging methods too blunt to address details of this complex process. Here, we contribute a means to explore whether individual liposomes become deformed upon binding to fluid cell-membrane mimics. This was accomplished by using hydrodynamic forces to control the propulsion of nanoscale liposomes electrostatically attracted to a supported lipid bilayer. In this way, the size of individual liposomes could be determined by simultaneously measuring both their individual drift velocity and diffusivity, revealing that for a radius of ∼45 nm, a close agreement with dynamic light scattering data was observed, while larger liposomes (radius ∼75 nm) displayed a significant deformation unless composed of a gel-phase lipid. The relevance of being able to extract this type of information is discussed in the context of membrane fusion and cellular uptake