Bulletin of the American Physical Society
60th Annual Meeting of the Divison of Fluid Dynamics
Volume 52, Number 12
Sunday–Tuesday, November 18–20, 2007; Salt Lake City, Utah
Session JD: Biofluids IX: Cellular |
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Chair: Amy Lang, University of Alabama Room: Salt Palace Convention Center 151 A-C |
Monday, November 19, 2007 3:35PM - 3:48PM |
JD.00001: A Stochastic Coarse-Grained Model of a Red Blood Cell Igor Pivkin, George Karniadakis A Red blood cell (RBC) can be modeled as a fluid volume enclosed by a flexible membrane. The membrane consists of a lipid bilayer and a protein skeleton, which determine the deformation behavior of the RBC. We develop a rigorous coarse-graining procedure for modeling the RBC membrane. The model takes into account the bending energy, in-plane shear energy, and constraints of fixed surface area and fixed enclosed volume. The coarse-grained model is validated against available experimental data and in Dissipative Particle Dynamics (DPD) simulations of the RBC in microcirculation. [Preview Abstract] |
Monday, November 19, 2007 3:48PM - 4:01PM |
JD.00002: Three-dimensional simulation of red blood cells in microcirculation Hong Zhao, Jonathan Freund The hydrodynamic interactions between blood cells are critical for understanding the hemodynamics in microcirculations. We perform a three-dimensional simulation based on the Stokes-flow boundary integral equations to study such systems. The red blood cells are modeled as three-dimensional elastic shells, being highly resistant to any surface dilatation but compliant to bending. The cell shape is approximated by truncated series of spherical harmonics; this spectral representation results in high numerical accuracy and rigorous dealiasing without adding any numerical dissipation. The moving velocities of cell surfaces are solved from a boundary integral equation. The periodic Stokes-flow Green's function is decomposed into a short-range point-to-point-interaction part and a long-range smooth Fourier part; the computational cost is made $O(N\log N)$ by using a $P^3M$ method. The no-slip boundary condition on the vessel wall is imposed by a penalty method, which enables simulating complex geometries with simple periodic Green's functions. Preliminary results include the deformation of a single cell in a shear flow and multiple cells through a blood vessel. [Preview Abstract] |
Monday, November 19, 2007 4:01PM - 4:14PM |
JD.00003: Computational Modeling and Simulation of Leukocyte Rolling Adhesion Vijay Pappu, Prosenjit Bagchi A 3D computational model is presented to simulate transient rolling adhesion and deformation of leukocytes over a selectin coated surface in shear flow. The model is based on immersed boundary method for cell deformation, and Monte Carlo simulation for receptor/ligand interaction. The model is shown to predict the characteristic `stop-and-go' motion of rolling leukocytes. We examine the effect of cell deformation, shear rate, and microvilli distribution on the rolling characteristics. We observe that compliant cells roll more stably, and have longer pauses due to reduced bond force and increased bond lifetime. Microvilli presentation is shown to affect rolling characteristics by altering the step size, but not pause times. Adhesion is seen to occur via multiple tethers, each of which forms multiple selectin bonds, but often one tether is sufficient to support rolling. The adhesion force is concentrated in only 1--3 tethered microvilli in the rear-most part of a cell. We also observe that the number of selectin bonds that hold the cell effectively against hydrodynamic shear is significantly less than the total adhesion bonds formed between a cell and the substrate. The force loading on individual microvillus and selectin bond is not continuous, rather occurs in steps. Further, we find that the peak force on a tethered microvillus is much higher than that measured to cause tether extrusion. [Preview Abstract] |
Monday, November 19, 2007 4:14PM - 4:27PM |
JD.00004: Micro-PIV Measurements of Pulsatile Flow Over Endothelial Cells. Chiamin Leong, Gary Nackman, Timothy Wei In both humans and mammals, endothelial cells remodel themselves according to mechanical loading by changing shape and orientation. Subsequently, these mechanical forces are transduced into chemical signals, mechanotransduction, involving changes in gene and protein expression. Alterations in mechanotransduction by endothelial cells to underlying smooth muscle cells is a key factor in human arterial disease. The goal of this study is to determine the importance of spatially and temporally varying mechanical loading and examine biological response under different flow conditions. In-vitro micro-PIV measurements are made in pulsatile flow over cultured endothelial cells flush mounted in a small rectangular channel. Cells are subjected to peak shear stress of 20 dynes/cm$^{2}$ corresponding to peak Re of 1000 and Womersley number of 1.4. Using multiple measurement planes, local surface height, surface pressure, and wall shear stress are extracted from the measurements. Simultaneous Raman spectroscopy is also being explored to investigate the bio-chemical response of live cultured human and bovine cells. [Preview Abstract] |
Monday, November 19, 2007 4:27PM - 4:40PM |
JD.00005: Combined measurements of flow-induced shear stress and gene expression of individual endothelial cells Massimiliano Rossi, Ralph Lindken, Beerend P. Hierck, Jerry Westerweel It is known that endothelial cells respond to the biomechanical forces induced by the blood flow by remodeling their shape. It is also postulated that different shear stress patterns modulate the gene expression of the cells. The mechanism by which they sense shear stress and the mechanotransduction pathway governing the blood-vessel wall interaction is still unknown and object of investigation. We used an optical, non-tactile measurement technique based on $\mu$PIV to investigate the relationship between shear stress distribution, shape and gene expression on a single-cell level. The cells are cultured in parallel flow chambers and subjected to different flow conditions. The fluid flow velocity in several planes over the cell is measured. From the three-dimensional flow field velocity profiles are extracted and used to reconstruct the cell topography and the shear stress distribution over it. This technique allows to achieve a spatial resolution of up to 1 $\mu$m attaining an average of 500 data points for each single cell. The gene expression measurements are performed with a shear responsive pKLF2-EGFP promoter construct transfected in the cells. Results will be shown on endothelial cells subjected to a steady flow inducing a nominal wall shear stress level of 1.5 Pa. [Preview Abstract] |
Monday, November 19, 2007 4:40PM - 4:53PM |
JD.00006: Modeling the deformation of a migrating cell adhering to a rigid ligand-coated substrate in the presence of a shear flow Keng-Hwee Chiam, Tan Lei Lai, Raymond Quek We have developed a computational model for the process in metastasis where tumor cells that have intravasated into the vasculature are carried by the circulation to a distant part of the body. Using a two-dimensional model of a cell as a homogeneous viscoelastic drop that is parametrized by its cytoplasmic viscosity and membrane surface tension, we have shown that the length of the cell membrane that is adhered to the substrate can be expressed in a very simple relation involving only the product of the inverse of the cell's capillary number and the distance that the cell has migrated. We have also shown that this relation may be exploited in determining a cell's cytoplasmic viscosity in terms of mechanical quantities such as adhered length and distance migrated. This may aid in the development of microfluidic devices that may one day serve as a diagnostic tool to screen for tumor cells that have a different stiffness from normal cells. Finally, we have also shown that, when the cell is sufficiently close to the rigid substrate, adhesive forces mediated by receptors on the cell and ligands on the substrate is negligible. We provide evidence for this by showing that the length of the cell membrane adhered to the substrate is independent of the density of adhesion receptors on the cell's membrane. [Preview Abstract] |
Monday, November 19, 2007 4:53PM - 5:06PM |
JD.00007: Bond tilting and sliding friction in a model of cell adhesion Sylvain Reboux, Giles Richardson, Oliver Jensen As a simple theoretical model of a cell adhering to a biological interface, we consider a rigid sphere moving in a viscous shear flow near a wall. Adhesion forces arise through intermolecular bonds between receptors on the cell and their ligands on the wall, which form flexible tethers that can stretch and tilt as the base of the cell moves past the wall; binding kinetics is assumed to follow a standard model for slip bonds. Our model reveals three distinct types of motion: either bonds accumulate at the peeling edge and slow down the cell almost to a halt; or bonds adhere strongly, but without creating any significant torque, and the cell tank-treads over the wall without slipping; or the cell moves near its free-stream speed with bonds providing weak frictional resistance to sliding. Under realistic conditions, the model predicts bistability among these three states, implying that at critical shear rates the system can switch abruptly between firm adhesion, tank-treading and free sliding. The model suggests that sliding friction arising through bond tilting may play a significant dynamical role in cell--adhesion applications such as neutrophil rolling and bacterial colonization under flow. [Preview Abstract] |
Monday, November 19, 2007 5:06PM - 5:19PM |
JD.00008: Formation of a cylindrical bridge in cell division Daniel Citron, Laura E. Schmidt, Elizabeth Reichl, Yixin Ren, Douglas Robinson, Wendy W. Zhang In nature, the shape transition associated with the division of a mother cell into two daughter cells proceeds via a variety of routes. In the cylinder-thinning route, which has been observed in {\it Dictyostelium} and most animal cells, the mother cell first forms a broad bridge-like region, also known as a furrow, between two daughter cells. The furrow then rapidly evolves into a cylindrical bridge, which thins and eventually severs the mother cell into two. The fundamental mechanism underlying this division route is not understood. Recent experiments on {\it Dictyostelium} found that, while the cylinder-thinning route persists even when key actin cross-linking proteins are missing, it is disrupted by the removal of force-generating myosin-II proteins. Other measurements revealed that mutant cells lacking myosin-II have a much more uniform tension over the cell surface than wild-type cells. This suggests that tension variation may be important. Here we use a fluid model, previously shown to reproduce the thinning dynamics [Zhang \& Robinson, PNAS {\bf 102}, 7186 (2005)], to test this idea. Consistent with the experiments, the model shows that the cylinder formation process occurs regardless of the exact viscoelastic properties of the cell. In contrast to the experiments, a tension variation in the model hinders, rather then expedites, the cylinder formation. [Preview Abstract] |
Monday, November 19, 2007 5:19PM - 5:32PM |
JD.00009: Dynamics of vesicles in electric fields Petia Vlahovska, Ruben Gracia Electromechanical forces are widely used for cell manipulation. Knowledge of the physical mechanisms underlying the interaction of cells and external fields is essential for practical applications. Vesicles are model cells made of a lipid bilayer membrane. They are examples of ``soft'' particles, i.e., their shape when subjected to flow or electric field is not given a priori but it is governed by the balance of membrane, fluid and electrical stresses. This generic ``softness'' gives rise to a very complex vesicle dynamics in external fields. In an AC electric field, as the frequency is increased, vesicles filled with a fluid less conducting than the surrounding fluid undergo shape transition from prolate to oblate ellipsoids. The opposite effect is observed with drops. We present an electro- hydrodynamic theory based on the leaky dielectric model that quantitatively describes experimental observations. We compare drops and vesicles, and show how their distinct behavior stems from different interfacial properties. [Preview Abstract] |
Monday, November 19, 2007 5:32PM - 5:45PM |
JD.00010: Statistical Analysis of the Chemotactic Motility Cycle of Amoeboid Cells B. Alonso-Latorre, J.C. del Alamo, R. Meili, J. Rodriguez-Rodriguez, R. A. Firtel, J.C. Lasheras Amoeboid motility results from the repetition of stereotypic steps that produce quasi-periodic oscillations of cell length and speed. We characterize the steps of the motility cycle of \textit{Dictyostelium }cells crawling on elastic substrates by analyzing their traction forces. Using a high-resolution force cytometry method for wild type cells and mutants with contractility and adhesion defects, we find that the time evolution of the traction forces is quasi-periodic, with a period (T) that correlates strongly with the cell speed (V) according to a simple law VT=L. The constant L is the distance traveled per cycle. The cellular traction forces are much larger than needed to overcome the viscous drag from the lubrication layer between the cells and the substrate, but they do not correlate with V. These results suggest that the speed of amoeboid migration is determined by the ability of the cell to repeat the steps of the motility cycle in a coordinated way. The phase average allowed us to combine time sequences of force maps derived from different cells to obtain a spatio-temporal representation of a canonical motility cycle divided into four steps: protrusion, contraction, retraction and relaxation. We find that myosin II-dependent contraction is present in all the steps of the wild-type motility cycle, including protrusion. JCA supported by MEC/Fulbright (Spain). [Preview Abstract] |
Monday, November 19, 2007 5:45PM - 5:58PM |
JD.00011: Diffusion Based Chemical Extraction from Cell Suspensions in Microchannels Ellen Longmire, Clara Mata, Katie Fleming, Allison Hubel Diffusion-based extraction of the cryoprotective agent dimethyl sulfoxide (DMSO) from blood suspensions offers distinct advantages over centrifugation, the conventional method of DMSO removal, most importantly, potential reductions in cell losses. To demonstrate diffusion-based extraction, laminar flows of two parallel streams, a cell suspension containing DMSO and a wash stream, were characterized experimentally. The streams entered a rectangular channel (500 $\mu $m x 25 mm x 125 mm) through opposing ports, and the transport of DMSO across the depth was studied as a function of cell suspension flow rate fraction and Peclet number (Pe). Visualization and concentration measurements were performed in the range 1000 $<$ Pe $<$ 10000 (1 $<$ Re $<$ 10). Measured concentration values in the outlet cell and wash streams matched closely with predictions from continuum simulations. Further, for appropriate suspension flow rates and flow rate fractions, cell recovery rates were very high, $\sim $95{\%}. The results suggest that diffusion methods are viable for processing of clinical-scale suspension volumes. [Preview Abstract] |
Monday, November 19, 2007 5:58PM - 6:11PM |
JD.00012: Computational Modeling of Cell Electroporation and Molecular Delivery. Hao Lin, Jianbo Li Electroporation is an elegant means to gain access to the cytoplasm, and to deliver molecules into the cell while simultaneously maintaining viability and functionality. In this technique, an applied electric pulse transiently permeabilizes the cell membrane, through which biologically active agents such as DNA, RNA, and amino acids can enter the cell, and to perform tasks such as gene and cancer therapy. Current electroporation technologies fall short of desired efficiency and reliability, in part due to the lack of a good understanding in the pertinent fundamental processes. In this work, we use computational modeling to investigate electroporation-mediated molecular delivery, with a focus on the transport mechanisms long ignored in previous studies. By coupling the Smoluchowski equation governing membrane permeabilization with an electrohydrodynamic model, major aspects including electrophoresis, diffusion, and membrane deformation are investigated. Specifically, the effect of electrical parameters such as field strength, duration, and intra-/extra-cellular electrical conductivity on transport efficacy will be quantified. The eventual objective of this study is to optimize molecular delivery via simultaneously increasing transport and minimizing cell damage due to field exposure. [Preview Abstract] |
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