FLUID SHEAR-STIMULATED DINOFLAGELLATE BIOLUMINESCENCE

Bioluminescence studies provide insight into the properties of water motion that are stimulatory to flow-sensitive organisms such as dinoflagellates, the most common sources of near-surface oceanic bioluminescence. Previous laboratory studies employing steady flows have characterized the luminescent response of dinoflagellates in terms of shear stress. In the present study, computational and experimental approaches were used to investigate the contributions of shear and acceleration to cells responding in a laminar converging flow field, where regions of high acceleration and shear are spatially separated. Flow-stimulated flashes by the dinoflagellates Lingulodinium polyedrum and Ceratocorys horrida were used as a near-instantaneous monitor of cell response. By combining video analysis of flash trajectories with computational methods, the location of each stimulated cell was determined and flow parameters at that location were calculated. Based on several criteria, shear stress was considered the flow parameter most stimulatory to cells. For both dinoflagellates species and for all flow rates, essentially all cells responded downstream near the wall where shear stress levels were maximal, and levels of acceleration and extensional stress were as much as two orders of magnitude less than locations away from the wall. Minimum shear stress levels at the cell positions were consistent with response thresholds based on previous studies. Bioluminescence is an excellent tool for examining how organisms respond to flow at the small temporal and spatial scales relevant to planktonic organisms.     

Crossflow microfiltration of animal cells

Laminar shear is the primary mechanism of cell damage, limiting flow rate (and hence flux) in crossflow microfiltration of animal cells. Sensitivity to hydrodynamic and interfacial stress is reduced by the addition of 0.1% Pluronic polyol. A critical average wall shear rate of 3000 s(-1) (above which damage occurs) is found for several cell types, including mammalian and insect cells. Hydrodynamic stress also limits the maximum tip speed in a rotary lobe pump to less than 350 cm/s. Turbulent flow in the recirculation loop piping at Reynolds numbers of up to 71,000 does not cause cell damage. Maximum sustainable flux decreases with cell concentration and increases with cell size (in qualitative agreement with the hydrodynamic lift model). A flux of 30 to 75 L/m(2) h (depending on cell size) can be sustained during 20-fold concentration from 2.5 x 10(6) cells/ml, while maintaining high cell viability.     

Pulsatile flow in a coronary artery using multiphase kinetic theory

Pulsatile flow in a model of a right coronary artery (RCA) was previously modeled as a single-phase fluid and as a two-phase fluid using experimental rheological data for blood as a function of hematocrit and shear rate. Here we present a multiphase kinetic theory model which has been shown to compute correctly the viscosity of red blood cells (RBCs) and their migration away from vessel walls: the Fahraeus–Lindqvist effect. The computed RBC viscosity decreases with shear rate and vessel size, consistent with measurements. The pulsatile computations were performed using a typical cardiac waveform until a limit cycle was well established. The RBC volume fractions, shear stresses, shear stress gradients, granular temperatures, viscosities, and phase velocities varied with time and position during each cardiac cycle. Steady-state computations were also performed and were found to compare well with time-averaged transient results. The wall shear stress and wall shear stress gradients (both spatial and temporal) were found to be highest on the inside area of maximum curvature. Potential atherosclerosis sites are identified using these computational results.     

Sonoporation from jetting cavitation bubbles

The fluid dynamic interaction of cavitation bubbles with adherent cells on a substrate is experimentally investigated. We find that the nonspherical collapse of bubbles near to the boundary is responsible for cell detachment. High-speed photography reveals that a wall bounded flow leads to the detachment of cells. Cells at the edge of the circular area of detachment are found to be permanently porated, whereas cells at some distance from the detachment area undergo viable cell membrane poration (sonoporation). The wall flow field leading to cell detachment is modeled with a self-similar solution for a wall jet, together with a kinetic ansatz of adhesive bond rupture. The self-similar solution for the delta-type wall jet compares very well with the full solution of the Navier-Stokes equation for a jet of finite thickness. Apart from annular sites of sonoporation we also find more homogenous patterns of molecule delivery with no cell detachment.     

小约化体积膜泡形状的研究

目的:研究ADE模型下小约化体积膜泡的形状。方法:应用数值计算方法中的打靶法,运用Mathematica 7.0软件进行编程。结果:在ADE模型下,计算得到了一系列小约化体积的膜泡的形状,解决了已往小约化体积区域内不存在稳定膜泡的问题。结论:研究表明,在ADE模型下通过适当的边界条件把黏附双层区域的接触势能考虑进去,数值计算结果与实验上的非常相似。     

Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels

Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cell (RBC) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation. RBC aggregation was modeled by a Morse potential function based on depletion-mediated assumption, and the adhesion of the CTC to the vessel wall was achieved by the interactions between receptors and ligands at the CTC and those at the endothelial cells forming the vessel wall. The results demonstrated that in the microvessel of \(15\,\upmu \hbox {m}\) diameter, the CTC has an increasing probability of adhesion with the hematocrit due to a growing wall-directed force, resulting in a larger number of receptor–ligand bonds formed on the cell surface. However, with the increase in microvessel size, an enhanced lift force at higher hematocrit detaches the initial adherent CTC quickly. If the microvessel is comparable to the CTC in diameter, CTC adhesion is independent of Hct. In addition, the velocity of CTC is larger than the average blood flow velocity in smaller microvessels and the relative velocity of CTC decreases with the increase in microvessel size. An increased blood flow resistance in the presence of CTC was also found. Moreover, it was found that the large deformation induced by high flow rate and the presence of aggregation promote the adhesion of CTC.     

Dependence of adhesive behavior of neutrophils on local fluid dynamics in a region with recirculating flow

We have recently described patterns of adhesion of different types of leukocytes downstream of a backward facing step. Here the predicted fluid dynamics in channels incorporating backward facing steps are described, and related to the measured velocities of flowing cells, patterns of attachment and characteristics of rolling adhesion for neutrophils perfused over P-selectin. Deeper (upstream depth 300 microm, downstream depth 600 microm, maximum wall shear stress approximately 0.1 Pa) and shallower (upstream depth 260 microm, downstream depth 450 microm, maximum wall shear stress approximately 0.3 Pa) channels were compared. Computational fluid dynamics (CFD) predicted the presence of vortices downstream of the steps, distances to reattachment of flow, local wall shear stresses and components of velocity parallel and perpendicular to the wall. Measurements of velocities of perfused neutrophils agreed well with predictions, and suggested that adhesion to P-selectin should be possible in the regions of recirculating flow, but not downstream in re-established flow in the high shear channel. When channels were coated with a P-selectin-Fc chimaera, neutrophils were captured from flow and immobilised. Capture showed local maxima around the reattachment points, but was absent elsewhere in the high shear chamber. In the low shear chamber there was depression of adhesion just beyond the reattachment point because of expansion of flow and depletion of neutrophils near the wall. Inside the recirculation zones, adhesion decreased approaching the step because of an increasing, vertically upward velocity component. When channels were coated with P-selectin, neutrophils rolled in all regions, but lifted off the surface as they rolled backwards into low shear regions near the step. Rolling velocity in the recirculation zone was independent of shear stress, possibly because of the effects of vertical lift. We conclude that while local wall shear stress influences adhesive behavior, delivery of cells to the wall and their behavior after capture also depend on components of flow perpendicular to the wall.     

Numerical analysis of the deformation of an adherent drop under shear flow

The adhesion of leukocytes to substrates is an important biomedical problem and has drawn extensive research. In this study, employing both single and compound drop models, we investigate how hydrodynamics interacts with an adherent liquid drop in a shear flow. These liquid drop models have recently been used to describe the rheological behavior of leukocytes. Numerical simulation confirms that the drop becomes more elongated when either capillary number or initial contact angle increases. Our results show that there exists a thin region between the drop and the wall as the drop undergoes large stretching, which allows high pressure to build up and provides a lift force. In the literature, existing models regard the leukocyte as a rigid body to calculate the force and torque acting on the drop in order to characterize the binding between cell receptors and endothelial ligands. The present study indicates that such a rigid body model is inadequate and the force magnitude obtained from it is less than half of that obtained using the deformable drop models. Furthermore, because of its much higher viscosity, the cell nucleus introduces a hydrodynamic time scale orders of magnitude slower than the cytoplasm. Hence the single and compound drops experience different dynamics during stretching, but exhibit very comparable steady-state shapes. The present work offers a framework to facilitate the development of a comprehensive dynamic model for blood cells.     

Particle Margination and Its Implications on Intravenous Anticancer Drug Delivery

“Margination” refers to the movement of particles in flow toward the walls of a channel. The term was first coined in physiology for describing the behavior of white blood cells (WBCs) and platelets in blood flow. The margination of particles is desirable for anticancer drug delivery because it results in the close proximity of drug-carrying particles to the endothelium, where they can easily diffuse into cancerous tumors through the leaky vasculature. Understanding the fundamentals of margination may further lead to the rational design of particles and allow for more specific delivery of anticancer drugs into tumors, thereby increasing patient comfort during cancer treatment. This paper reviews existing theoretical and experimental studies that focus on understanding margination. Margination is a complex phenomenon that depends on the interplay between inertial, hydrodynamic, electrostatic, lift, van der Waals, and Brownian forces. Parameters that have been explored thus far include the particle size, shape, density, stiffness, shear rate, and the concentration and aggregation state of red blood cells (RBCs). Many studies suggested that there exists an optimal particle size for margination to occur, and that nonspherical particles tend to marginate better than spherical particles. There are, however, conflicting views on the effects of particle density, stiffness, shear rate, and RBCs. The limitations of using the adhesion of particles to the channel walls in order to quantify margination propensity are explained, and some outstanding questions for future research are highlighted.     

Model of Red Blood Cell Rotation in the Flow toward a Cell Sizing Orifice: Application to Volume Distribution

The rotation of human red blood cells (RBC) as they flow in the shear field established by a Coulter type orifice is modeled. This model, based on hydrodynamics of ellipsoid rotation in laminar creeping flow, is used to calculate the probability of the cells entering the orifice with a specific orientation. The electrical resistance change produced by a cell passing through the orifice of an electronic cell volume detector is the product of an orientation-dependent shape factor and the cell volume. This paper presents a method to calculate the shape factor probability distribution which can be used to predict its effect on the cell volume distribution. Experimental results confirm the theoretical prediction that the right skewness of resistance change distributions is in part a result of the nonspherical shape of red cells.     

The effect of blood viscoelasticity on pulsatile flow in stationary and axially moving tubes

An analytical solution for pulsatile flow of a generalized Maxwell fluid in straight rigid tubes, with and without axial vessel motion, has been used to calculate the effect of blood viscoelasticity on velocity profiles and shear stress in flows representative of those in the large arteries. Measured bulk flow rate Q waveforms were used as starting points in the calculations for the aorta and femoral arteries, from which axial pressure gradient ▿P waves were derived that would reproduce the starting Q waves for viscoelastic flow. The ▿P waves were then used to calculate velocity profiles for both viscoelastic and purely viscous flow. For the coronary artery, published ▿P and axial vessel acceleration waveforms were used in a similar procedure to determine the separate and combined influences of viscoelasticity and vessel motion.Differences in local velocities, comparing viscous flow to viscoelastic flow, were in all cases less than about 2% of the peak local velocity. Differences in peak wall shear stress were less than about 3%.In the coronary artery, wall shear stress differences between viscous and viscoelastic flow were small, regardless of whether axial vessel motion was included. The shape of the wall shear stress waveform and its difference, however, changed dramatically between the stationary and moving vessel cases. The peaks in wall shear stress difference corresponded with large temporal gradients in the combined driving force for the flow.     

Chirality‐specific lift forces of helix under shear flows: Helix perpendicular to shear plane

Chiral objects in shear flow experience a chirality‐specific lift force. Shear flows past helices in a low Reynolds number regime were studied using slender‐body theory. The chirality‐specific lift forces in the vorticity direction experienced by helices are dominated by a set of helix geometry parameters: helix radius, pitch length, number of turns, and helix phase angle. Its analytical formula is given. The chirality‐specific forces are the physical reasons for the chiral separation of helices in shear flow. Our results are well supported by the latest experimental observations.     

Diffusion of microspheres in shear flow near a wall: use to measure binding rates between attached molecules.

The rate and distance-dependence of association between surface-attached molecules may be determined by monitoring the motion of receptor-bearing spheres along ligand-coated surfaces in a flow chamber (Pierres et al., Proc. Natl. Acad. Sci. U.S.A. 95:9256-9261, 1998). Particle arrests reveal bond formation, and the particle-to-surface distance may be estimated from the ratio between the velocity and the wall shear rate. However, several problems are raised. First, data interpretation requires extensive computer simulations. Second, the relevance of standard results from fluid mechanics to micrometer-size particles separated from surfaces by nanometer distances is not fully demonstrated. Third, the wall shear rate must be known with high accuracy. Here we present a simple derivation of an algorithm permitting one to simulate the motion of spheres near a plane in shear flow. We check that theoretical predictions are consistent with the experimental dependence of motion on medium viscosity or particle size, and the requirement for equilibrium particle height distribution to follow Boltzman's law. The determination of the statistical relationship between particle velocity and acceleration allows one to derive the wall shear rate with 1-s(-1) accuracy and the Hamaker constant of interaction between the particle and the wall with a sensitivity better than 10(-21) J. It is demonstrated that the correlation between particle height and mean velocity during a time interval Deltat is maximal when Deltat is about 0.1-0.2 s for a particle of 1.4-microm radius. When the particle-to-surface distance ranges between 10 and 40 nm, the particle height distribution may be obtained with a standard deviation ranging between 8 and 25 nm, provided the average velocity during a 160-ms period of time is determined with 10% accuracy. It is concluded that the flow chamber allows one to detect the formation of individual bonds with a minimal lifetime of 40 ms in presence of a disruptive force of approximately 5 pN and to assess the distance dependence within the tens of nanometer range.     

Wall shear rate measurements in an elastic curved artery model

Since atherosclerotic lesions tend to be localized at bends and branching points, knowledge of wall shear rate patterns in models of these geometries may help elucidate the mechanism of atherogenesis. This study uses the photochromic method of flow visualization to determine both the mean and amplitude of the wall shear rate waveform in straight and curved elastic arterial models to demonstrate the effects of curvature, elasticity, and the phase angle between the flow and pressure waveforms (impedance phase angle). Under sinusoidal flow conditions characteristic of large arteries, the mean shear rate at the inner wall of the curved tube is reduced 40–56% from its steady flow value, depending on the phase angle. Wall shear rate amplitudes in the curved tube are significantly reduced by wall motion (36–55% of the Womersley amplitude for a straight rigid tube). The shear rate amplitude at the outer wall decreases 30% as the phase angle is reduced from −20° to −66°, while the shear rate amplitude at the inner wall increases 45%. As a result, the oscillatory nature of flow at the outer wall decreases with decreasing negative phase angle, but flow at the inner wall becomes much more oscillatory. At large negative phase angles, characteristic of hypertension or vasoactive agents, the shear rate at the inner wall has a small mean and cycles through positive and negative values; the shear rate at the outer wall remains positive throughout the flow cycle. Thus, the impedance phase angle could affect atherogenesis along the inner wall if temporal and directional changes in wall shear rate play a role.     

An Investigation on Platelet Transport during Thrombus Formation at Micro-Scale Stenosis

This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke.     

An integrated fluid–structure interaction and thrombosis model for type B aortic dissection

False lumen thrombosis (FLT) in type B aortic dissection has been associated with the progression of dissection and treatment outcome. Existing computational models mostly assume rigid wall behavior which ignores the effect of flap motion on flow and thrombus formation within the FL. In this study, we have combined a fully coupled fluid–structure interaction (FSI) approach with a shear-driven thrombosis model described by a series of convection–diffusion reaction equations. The integrated FSI-thrombosis model has been applied to an idealized dissection geometry to investigate the interaction between vessel wall motion and growing thrombus. Our simulation results show that wall compliance and flap motion can influence the progression of FLT. The main difference between the rigid and FSI models is the continuous development of vortices near the tears caused by drastic flap motion up to 4.45 mm. Flap-induced high shear stress and shear rates around tears help to transport activated platelets further to the neighboring region, thus speeding up thrombus formation during the accelerated phase in the FSI models. Reducing flap mobility by increasing the Young’s modulus of the flap slows down the thrombus growth. Compared to the rigid model, the predicted thrombus volume is 25% larger using the FSI-thrombosis model with a relatively mobile flap. Furthermore, our FSI-thrombosis model can capture the gradual effect of thrombus growth on the flow field, leading to flow obstruction in the FL, increased blood viscosity and reduced flap motion. This model is a step closer toward simulating realistic thrombus growth in aortic dissection, by taking into account the effect of intimal flap and vessel wall motion.

     

The effect of compliance on wall shear in casts of a human aortic bifurcation

Rigid and compliant casts of a human aortic bifurcation were subjected to physiologically realistic pulsatile fluid flows. At a number of sites near the wall in the approximate median plane of the bifurcation of these models, fluid velocity was measured with a laser Doppler velocimeter, and wall motion (in the case of the compliant cast) was determined with a Reticon linescan camera. The velocity and wall motion data were combined to estimate the instantaneous shear rates at the cast wall. Analysis showed that at the outer walls the cast compliance reduced shear rates, while at the walls of the flow divider the shear rate was increased.     

A numerical analysis of forces exerted by laminar flow on spreading cells in a parallel plate flow chamber assay

Exposure of spreading anchorage-dependent cells to laminar flow is a common technique to measure the strength of cell adhesion. Since cells protrude into the flow stream, the force exerted by the fluid on the cells is a function of cell shape. To assess the relationship between cell shape and the hydrodynamic force on adherent cells, we obtained numerical solutions of the velocity and stress fields around bovine aortic endothelial cells during various stages of spreading and calculated the force required to detach the cells. Morphometric parameters were obtained from light and scanning electron microscopy measurements. Cells were assumed to have a constant volume, but the surface area increased during spreading until the membrane was stretched taut. Two-dimensional models of steady flow were generated using the software packages ANSYS (mesh generation) and FIDAP (problem solution). The validity of the numerical results was tested by comparison with published results for a semicircle in contact with the surface. The drag force and torque were greatest for round cells making initial contact with the surface. During spreading, the drag force and torque declined by factors of 2 and 20, respectively. The calculated forces and moments were used in adhesion models to predict the wall shear stress at which the cells detached. Based upon published values for the bond force and receptor number, round cells should detach at shear stresses between 2.5 and 6 dyn/cm(2), whereas substantially higher stresses are needed to detach spreading and fully spread cells. Results from the simulations indicate that (1) the drag force varies little with cell shape whereas the torque is very sensitive to cell shape, and (2) the increase in the strength of adhesion during spreading is due to increased contact area and receptor densities within the contact area. (c) 1993 John Wiley & Sons, Inc.     

Design of bio-mimetic particles with enhanced vascular interaction

The majority of particle-based delivery systems for the ‘smart’ administration of therapeutic and imaging agents have a spherical shape, are made by polymeric or lipid materials, have a size in the order of few hundreds of nanometers and a negligibly small relative density to aqueous solutions. In the microcirculation and deep airways of the lungs, where the creeping flow assumption holds, such small spheres move by following the flow stream lines and are not affected by external volume force fields. A delivery system should be designed to drift across the stream lines and interact repeatedly with the vessel walls, so that vascular interaction could be enhanced. The numerical approach presented in [Gavze, E., Shapiro, M., 1997. Particles in a shear flow near a solid wall: effect of nonsphericity on forces and velocities. International Journal of Multiphase Flow 23, 155–182.] is, here, proposed as a tool to analyze the dynamics of arbitrarily shaped particles in a creeping flow, and has been extended to include the contribution of external force fields. As an example, ellipsoidal particles with aspect ratio 0.5 are considered. In the absence of external volume forces, a net lateral drift (margination) of the particles has been observed for Stokes number larger than unity (St>1); whereas, for smaller St, the particles oscillate with no net lateral motion. Under these conditions, margination is governed solely by particle inertia (geometry and particle-to-fluid density ratio). In the presence of volume forces, even for fairly small St, margination is observed but in a direction dictated by the external force field. It is concluded that a fine balance between size, shape and density can lead to EVI particles (particles with enhanced vascular interaction) that are able to sense endothelial cells for biological and biophysical abnormalities, mimicking circulating platelets and leukocytes.     

Radial artery wall shear stress evaluation in patients with arteriovenous fistula for hemodialysis access

It has been extensively documented that changes in blood flow induce vascular remodeling and this phenomenon seems to be correlated to the shear forces imposed on the vessel wall by motion of blood. Wall shear stress, the tractive force that acts on the endothelium, has been shown to influence endothelial cell function. To study changes in wall shear stress that develop on the vessel wall upon changes of blood flow, we set up a technique that allows estimation of shear stress in the radial artery of patients on chronic hemodialysis therapy. The technique is based on color-flow Doppler examination of the radial artery before and after surgical creation of radiocephalic fistula for hemodialysis. Calculation of time function wall shear stress and blood flow rate in the radial artery is performed on the basis of arterial diameter, center-line velocity waveform and blood viscosity, using a numerical method developed according to Womersley's theory for pulsatile flow in tubes. The results presented confirm that the model developed is suitable for calculation of the wall shear stress that develops in the radial artery of patients before and after surgical creation of an arteriovenous fistula for hemodialysis. This methodology was developed for characterization of wall shear stress in the radial artery but may be well applied to other vessels that can be examined by echo-Doppler technique.