Damir B. Khismatullin

Radial oscillations of encapsulated microbubbles in viscoelastic liquids

The small-amplitude radial oscillations of a gas microbubble encapsulated by a viscoelastic solid shell and surrounded by a slightly compressible viscoelastic liquid are studied theoretically. The Kelvin–Voigt and 4-constant Oldroyd models are used to describe the viscoelastic properties of the shell and liquid, respectively. The equation for radial oscillation is derived using the method of matched asymptotic expansions. Based on this equation, we present the expressions for damping coefficients and scattering cross sections at the fundamental frequency and at twice that frequency. The numerical maximization of the amplitude-frequency response function shows that the resonance frequency for the encapsulated microbubble highly depends on viscous damping, and therefore, significantly differs from the undamped natural frequency. The effects of the shell and liquid parameters on the resonance frequency and scattering cross sections are analyzed.

Three-dimensional numerical simulation of receptor-mediated leukocyte adhesion to surfaces: Effects of cell deformability and viscoelasticity

Computational fluid dynamics is used to investigate the effects of cell deformability and viscoelasticity on receptor-mediated leukocyte adhesion to endothelium or a ligand coated surface in a parallel-plate flow chamber. In the three-dimensional numerical code, a leukocyte is modeled as a compound viscoelastic drop (a nucleus covered by a thick layer of cytoplasm). The nucleus, cytoplasm, and extracellular fluid are considered as Newtonian or viscoelastic liquids of high viscosity. The receptor-ligand interaction is incorporated into the code by using the spring-peeling kinetic model under the assumption that leukocyte receptors are located on the tips of cylindrical microvilli distributed over the leukocyte membrane. The code is based on the volume-of-fluid method, and the Giesekus constitutive equation is implemented in the code to capture viscoelasticity of the cytoplasm and nucleus. Numerical simulations demonstrate the formation and breakup of membrane tethers observed in vitro and suggest that the ...

Resonance frequency of microbubbles: Effect of viscosity

The transmitted frequency at which a gas bubble of millimeter or submillimeter size oscillates resonantly in a low-viscosity liquid is approximately equal to the undamped natural frequency (referred to as the Minnaert frequency if surface tension effects are disregarded). Based on a theoretical analysis of bubble oscillation, this paper shows that such an approximation cannot be validated for microbubbles used in contrast-enhanced ultrasound imaging. The contrast-agent microbubbles represent either encapsulated bubbles of size less than 10 microm or free (nonencapsulated) bubbles of submicron size. The resonance frequency of the microbubbles deviates significantly from the undamped natural frequency over the whole range of microbubble sizes due to the increased viscous damping coefficient. The difference between these two frequencies is shown to have a tremendous impact on the resonant backscatter by the microbubbles. In particular, the first and second harmonics of the backscattered signal from the microbubbles are characterized by their own resonance frequencies, equal to neither the microbubble resonance frequency nor the undamped natural frequency.

Leukocyte Rolling on P-Selectin: A Three-Dimensional Numerical Study of the Effect of Cytoplasmic Viscosity

Rolling leukocytes deform and show a large area of contact with endothelium under physiological flow conditions. We studied the effect of cytoplasmic viscosity on leukocyte rolling using our three-dimensional numerical algorithm that treats leukocyte as a compound droplet in which the core phase (nucleus) and the shell phase (cytoplasm) are viscoelastic fluids. The algorithm includes the mechanical properties of the cell cortex by cortical tension and considers leukocyte microvilli that deform viscoelastically and form viscous tethers at supercritical force. Stochastic binding kinetics describes binding of adhesion molecules. The leukocyte cytoplasmic viscosity plays a critical role in leukocyte rolling on an adhesive substrate. High-viscosity cells are characterized by high mean rolling velocities, increased temporal fluctuations in the instantaneous velocity, and a high probability for detachment from the substrate. A decrease in the rolling velocity, drag, and torque with the formation of a large, flat contact area in low-viscosity cells leads to a dramatic decrease in the bond force and stable rolling. Using values of viscosity consistent with step aspiration studies of human neutrophils (5-30 Pa·s), our computational model predicts the velocities and shape changes of rolling leukocytes as observed in vitro and in vivo.

Inertia-induced breakup of highly viscous drops subjected to simple shear

We investigate the inertia-driven breakup of viscous drops suspended in a less viscous liquid under simple shear. For Stokes flow, it is known that there is a critical value of the viscosity ratio, beyond which breakup does not occur. We find that for viscosity ratios larger than this, inertia can be used as a mechanism of breakup. Inertia increases the angle of tilt of the drops and effectively leads to emulsification for a wider range of viscosity ratios than in Stokes flow.

Oxidized Low-Density Lipoprotein Contributes to Atherogenesis via Co-activation of Macrophages and Mast Cells

Oxidized low-density lipoprotein (OxLDL) is a risk factor for atherosclerosis, due to its role in endothelial dysfunction and foam cell formation. Tissue-resident cells such as macrophages and mast cells release inflammatory mediators upon activation that in turn cause endothelial activation and monocyte adhesion. Two of these mediators are tumor necrosis factor (TNF)-α, produced by macrophages, and histamine, produced by mast cells. Static and microfluidic flow experiments were conducted to determine the number of adherent monocytes on vascular endothelium activated by supernatants of oxLDL-treated macrophages and mast cells or directly by oxLDL. The expression of adhesion molecules on activated endothelial cells and the concentration of TNF-α and histamine in the supernatants were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. A low dose of oxLDL (8 μg/ml), below the threshold for the clinical presentation of coronary artery disease, was sufficient to activate both macrophages and mast cells and synergistically increase monocyte-endothelium adhesion via released TNF-α and histamine. The direct exposure of endothelial cells to a much higher dose of oxLDL (80 μg/ml) had less effect on monocyte adhesion than the indirect activation via oxLDL-treated macrophages and mast cells. The results of this work indicate that the co-activation of macrophages and mast cells by oxLDL is an important mechanism for the endothelial dysfunction and atherogenesis. The observed synergistic effect suggests that both macrophages and mast cells play a significant role in early stages of atherosclerosis. Allergic patients with a lipid-rich diet may be at high risk for cardiovascular events due to high concentration of low-density lipoprotein and histamine in arterial vessel walls.

Sound-ultrasound interaction in bubbly fluids: Theory and possible applications

The interaction between sound and ultrasound waves in a weakly compressible viscous liquid with gas bubbles is considered. Using the method of multiple scales one- and two-dimensional nonlinear interaction equations are derived. The degeneracy of the interaction is found in bubbly fluids. This phenomenon lies in the fact that the interaction coefficients vanish at a certain frequency of ultrasound. We demonstrate that the integrable Davey–Stewartson I (DSI) system of equation can describe the two-dimensional sound-ultrasound evolution. The DSI equations are remarkable by their solutions referred to as dromions. In bubbly fluids the dromion represents the localized focused ultrasound wave which can alter the direction of its motion under changes in the boundary conditions for the sound wave. The condition of singular focusing of ultrasound in bubbly fluids is obtained. By numerical analysis of the interaction models, we reveal such processes as intensification of ultrasound by sound, nonlinear instability ...

Lipopolysaccharide induces the interactions of breast cancer and endothelial cells via activated monocytes

The adhesion of circulating cancer cells to vascular endothelium is a key step in hematogenous metastasis. Cancer cell-endothelium interactions are mediated by cell adhesion molecules that can also be involved in the arrest of monocytes and other circulating leukocytes on endothelium in inflammation. Static and microfluidic flow adhesion assays as well as flow cytometry were conducted in this study to elucidate the role of monocytes, bacterial lipopolysaccharide (LPS), and histamine in breast cancer cell adhesion to vascular endothelial cells. Tumor necrosis factor-α (TNF-α) released from LPS-treated monocytes triggered the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Histamine augmented the TNF-α effect, leading to a high number of arrested breast cancer cells under both static and shear flow conditions. LPS-treated monocytes were shown to enhance the arrest of breast cancer cells by anchoring the cancer cells to activated endothelial cells. This anchorage was achieved by binding cancer cell ICAM-1 to monocyte β2 integrins and binding endothelial ICAM-1 and VCAM-1 to monocyte β1 and β2 integrins. The results of this study imply that LPS is an important risk factor for cancer metastasis and that the elevated serum level of histamine further increases the risk of LPS-induced cancer metastasis. Preventing bacterial infections is essential in cancer treatment, and it is particularly vital for cancer patients affected by allergy.

Synergistic Effect of Histamine and TNF-α on Monocyte Adhesion to Vascular Endothelial Cells

The histamine level is high during allergic attacks, and patients with allergy may have chronic inflammatory conditions at which tumor necrosis factor (TNF)-α is extensively released by macrophages. Here, in vitro static and microfluidic flow assays were conducted to investigate the combined influence of histamine and TNF-α on adhesion of monocytic THP-1 cells to human umbilical vein endothelial cells (HUVEC). In a static assay, histamine stimulation of TNF-α-activated HUVEC elevated the number of attached THP-1 cells. In a flow assay, the number of crawling and firmly adherent THP-1 cells was higher on TNF-α + histamine activated HUVEC than on HUVEC activated by TNF-α alone. This synergistic effect of histamine and TNF-α is caused by the increased endothelial surface expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Since the exposure of TNF-α-activated endothelium to histamine favors monocyte recruitment, it may be a serious risk factor for atherosclerosis and other inflammatory disorders.

Chapter 3 The Cytoskeleton and Deformability of White Blood Cells

Publisher Summary White blood cells (WBCs) are the cellular elements of the immune system in humans and other animals. Their primary function is to patrol the body for potential sources of infection and destroy invading pathogens, such as viruses, bacteria, fungi, and parasitic microorganisms. Leukocytes derive from pluripotent hematopoietic stem cells in the bone marrow and are specialized into four morphologically different cell types of myeloid lineage (neutrophils, eosinophils, basophils, and monocytes) and lymphoid cells that include natural killer (NK) cells and T- and B-lymphocytes. WBCs, also known as “leukocytes,” migrate to the sites of infection to destroy pathogenic microorganisms. The ability of WBCs to deform is essential for this function, but it is also an important determinant of healthy vasculature. This chapter analyzes the effects of leukocyte deformability on leukocyte–endothelial interactions, presents the evidence for the critical role of the cytoskeleton in bulk mechanical properties of leukocytes, summarizes recent advances in rheological measurements of leukocytes, and discusses pathologies associated with leukocyte activation and reduced deformability of these cells.