Bulletin of the American Physical Society
2008 APS March Meeting
Volume 53, Number 2
Monday–Friday, March 10–14, 2008; New Orleans, Louisiana
Session Q16: Focus Session: Cytoskeletal Dynamics and Cell Motility II |
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Sponsoring Units: DBP DPOLY DFD Chair: Jay Tang, Brown University Room: Morial Convention Center 208 |
Wednesday, March 12, 2008 11:15AM - 11:51AM |
Q16.00001: Cell migration through connective tissue in 3-D Invited Speaker: A prerequisite for metastasis formation is the ability of tumor cells to invade and migrate through connective tissue. Four key components endow tumor cells with this ability: secretion of matrix-degrading enzymes, firm but temporary adhesion onto connective tissue fibers, contractile force generation, and rapid remodeling of cytoskeletal structures. Cell adhesion, contraction, and cytoskeletal remodeling are biomechanical parameter that can be measured on single cells using a panel of biophysical methods. We use 2-D and 3-D traction microscopy to measure contractile forces; magnetic tweezer microrheology to estimate adhesion strengths, cytoskeletal stiffness and molecular turn-over rates; and nanoscale particle tracking to measure cytoskeletal remodeling. On a wide range of tumor cell lines we could show that cell invasiveness correlates with increased expression of integrin adhesion receptors, increased contractile force generation, and increased speed of cytoskeletal reorganization. Each of those biomechanical parameters, however, varied considerably between cell lines of similar invasivity, suggesting that tumor cells employ multiple invasion strategies that cannot be unambiguously characterized using a single assay. [Preview Abstract] |
Wednesday, March 12, 2008 11:51AM - 12:03PM |
Q16.00002: Dynamics of active cellular response under stress Rumi De, Assaf Zemel, Samuel Safran Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. \textbf{Reference:} Nature Physics, vol. 3, pp 655 (2007). [Preview Abstract] |
Wednesday, March 12, 2008 12:03PM - 12:15PM |
Q16.00003: Observation of Non-local Mechanical Responses to Locally Applied Forces in Cells using Magnetic Micropost Arrays Corinne Lamb, Yaohua Liu, Daniel Reich, Nathan Sniadecki, Christopher Chen The process of force transduction by living cells is linked to changes in cellular function. To study the cellular response to applied forces, we have developed a novel force detection device, which can also be used to apply external forces to a cell. Cells are cultured atop an array of micrometer scale elastomeric posts, which act as independent sensors to cellular traction forces. An external force is applied to the adherent surface of the cell via a magnetic torque on a cobalt nanowire embedded in a single post. Results measuring the spatially resolved forces exerted by the cell over time indicate two responses: a sudden or a gradual global relaxation of the cell in response to a single force actuation. \footnote{N. Sniadecki, et. al, ``Magnetic microposts as an approach to apply forces to living cells,'' \emph{Proc Natl Acad Sci}, 104, no. 37 (2007): 14553} In both cases, the subcellular distribution of loss in traction forces was not concentrated near the point of stimulation but occurred instead at discrete locations around the cell's periphery. Observation of these adaptive non-local responses is potentially important in understanding how external forces are transduced into biochemical regulators of cell function. [Preview Abstract] |
Wednesday, March 12, 2008 12:15PM - 12:27PM |
Q16.00004: Substrate Stiffness Detection by Cellular Stress and Strain Shang-You Tee, Paul Janmey Cells can detect the stiffness of their microenvironment and use this elasticity information to perform cellular functions. We grow cells in hydrogels of different stiffnesses. We embed particles in the hydrogels and measure the traction forces exerted on the hydrogel by tracking particle motions. We correlate these motions to protein dynamics and deduce the stress-strain relationship that cells use to measure elasticity. [Preview Abstract] |
Wednesday, March 12, 2008 12:27PM - 12:39PM |
Q16.00005: Probing Eukaryotic Chemotaxis with Optically Manipulated Biomimetic Microparticles. Holger Kress, Cecile Mejean, Jin Gyu Park, Tarek Fahmy, Eric Dufresne Chemotactic cells are able to sense chemical gradients and to move towards the source of a chemical agent. Eukaryotic chemotaxis is an important part of the mammalian immune system and poses many questions about the cell's physical mechanisms to detect, process and respond to external stimuli. While an understanding of this process is emerging, new methods for precise, controlled and flexible quantitative cell stimulation are needed to test existing hypotheses. We present such a method which is based on optically manipulated biomimetic microparticles. We are developing colloidal particles that provide controlled release of a chemoattractant. These micro-sources of stimulating agents are positioned with optical tweezers at arbitrary locations close to chemotactic cells in order to apply flexible spatio-temporal stimulation patterns to the cells. We show that chemotactic cell response - directed cell polarization, motility and turning - can be induced by our novel stimulation method. In conjunction with live cell microscopy this method is suitable to study the dynamics of intracellular signaling loops. [Preview Abstract] |
Wednesday, March 12, 2008 12:39PM - 12:51PM |
Q16.00006: Quantifying \textit{Dictyostelium discoideum} Aggregation Colin McCann, Paul Kriebel, Carole Parent, Wolfgang Losert Upon nutrient deprivation, the social amoebae \textit{Dictyostelium discoideum} enter a developmental program causing them to aggregate into multicellular organisms. During this process cells sense and secrete chemical signals, often moving in a head-to-tail fashion called a `stream' as they assemble into larger entities. We measure \textit{Dictyostelium} speed, shape, and directionality, both inside and outside of streams, and develop methods to distinguish group dynamics from behavior of individual cells. We observe an overall increase in speed during aggregation and a decrease in speed fluctuations once a cell joins a stream. Initial results indicate that when cells are in close proximity the trailing cells migrate specifically toward the backs of leading cells. [Preview Abstract] |
Wednesday, March 12, 2008 12:51PM - 1:03PM |
Q16.00007: Cell motility as a persistent random walk Simon Norrelykke, Frank Julicher We study the stochastic properties of trajectories of individual keratocytes that move on a solid substrate. The distribution of observed velocities exhibits a characteristic maximum at finite speed and a local minimum at zero velocity. This velocity distribution depends on the averaging time during which velocities are measured. To characterize the stochatsic properties of the system, we determine the correlations between longitudinal and transverse components of the acceleration with the instantaneous velocity. The experimental data can be captured by a simplified physical description of cell locomotion where random forces act on a system of two elastically coupled elements, one of which is driven forward by an active process, dragging the second behind. [Preview Abstract] |
Wednesday, March 12, 2008 1:03PM - 1:15PM |
Q16.00008: Role of receptor patch geometry for cell adhesion in hydrodynamic flow Christian Korn, Ulrich Schwarz Motivated by the physiological and biotechnological importance of cell adhesion under hydrodynamic flow, we theoretically investigate the efficiency of initial binding between a receptor-coated sphere and a ligand-coated wall in linear shear flow. Using a Langevin equation that accounts for both hydrodynamic interactions and Browian motion, we numerically calculate the mean first passage time (MFPT) for receptor-ligand encounter. We study how the MFPT is influenced by flow rate, receptor and ligand coverage, and receptor patch geometry. With increasing shear rate, the MFPT decreases monotonically. Above a threshold value of a few hundreds, binding efficiency is enhanced only weakly upon increasing the number of receptor patches. Increasing the height of the receptor patches increases binding efficiency much more strongly than increasing their lateral size. This strong dependance on out-off-plane geometry explains why white blood cells adhere to the vessel walls through receptor patches localized to the tips of microvilli, and why malaria-infected red blood cells form elevated receptor patches (\textit{knobs}). [1] C.~Korn and U.~S. Schwarz, \textit{Phys. Rev. Lett.} \textbf{97}: 138103, 2006. [2] C.~B. Korn and U.~S. Schwarz. \textit{J. Chem. Phys.} \textbf{126}: 095103, 2007 [Preview Abstract] |
Wednesday, March 12, 2008 1:15PM - 1:27PM |
Q16.00009: Dynamic friction measurements on living HeLa cells Marc-Antoni Goulet, Marie-Jos\'ee Colbert, Kari Dalnoki-Veress The interaction of cells with various interfaces, and especially man-made surfaces, is an active field of research. In our experiment we use a micropipette to measure both the friction and normal force as a cell slides across a surface. A thin substrate, coated with Poly-L-Lysine is brought into contact with a HeLa cell. The adjustable substrate motion is used to study the response of the cell at various normal forces and speeds. Analysis of the micropipette provides dynamic measurements of both the friction and normal force. With our novel setup we are able to probe the attachment/detachment process of living cells. [Preview Abstract] |
Wednesday, March 12, 2008 1:27PM - 1:39PM |
Q16.00010: AFM method to study mechanics of biological cells with real brushy surface. Igor Sokolov, Swaminathan Iyer, Ravi Gaikwad, Venkatesh Subba-Rao, Craig Woodworth AFM is particular useful for studying biological systems because it can be used on viable cells directly in physiological media. Most of the time, the deformation curves measured with AFM on cells have typical ``two layer'' behavior. As we see from confocal fluorescent images of cells, the cell surface is not flat and covered by a brush-like structure. Here we describe a simple two-layer model to decouple the force response of these two ``layers'', the cell body and brush. In contrast with the existent biological methods, AFM is a highly sensitive technique that can provide precise quantitative data on both lengths and grafting densities of the brush while measured directly on viable cells. Moreover, it allows one to decouple true cell rigidity from the contribution of the brush layer. This novel method can be applied to virtually any kind of cells. Ignoring this layer may result in incorrect values of cell rigidity derived from the AFM measurements. We demonstrate the developed method on the example of cancerous and normal human cervical cells. [Preview Abstract] |
Wednesday, March 12, 2008 1:39PM - 1:51PM |
Q16.00011: Dynamical measurement of the physical properties of single cells Marie-Josee Colbert, Cecile Fradin, Kari Dalnoki-Veress The mechanical response of living cells to external forces has attracted the attention of many researchers. We have developed a new tool that takes advantage of an `L' shaped micropipette to micromanipulate a single cell and put it in contact with an adhesive surface mounted on a translation stage. The spring constant of the micropipette is carefully measured and its deflection is used to apply a calibrated force, and probe the mechanical properties of the cell. As the cell is compressed between the pipette and substrate, dynamical measurements of the elasticity of the cell and the adhesion of the membrane to the substrate are obtained by monitoring the displacement of the micropipette. This technique gives access to real time monitoring of the cell response to a constant applied force, thus exploring the relaxation processes of the cell when subjected to deformation. [Preview Abstract] |
Wednesday, March 12, 2008 1:51PM - 2:03PM |
Q16.00012: Computational modeling of cell-cell adhesion and cell-endothelium peeling Keng-Hwee Chiam, Raymond Quek We describe the use of computational modeling to study the behavior of cells adhering to one another as well as to the circulatory endothelium. These cells are subjected to shear stress imposed by the circulatory plasma, and may peel from the endothelium as a result. Cells that peel have a higher chance to enter circulation and hence pose a greater threat in cancer metastasis. We use the immersed interface method to model the cells and solve for its biomechanical response. We quantitatively study the peeling dynamics as a function of the cells' material properties and the surrounding fluid's dynamics. We show how cell peeling from the endothelium is hampered by its adhesive interaction with surrounding cells. In addition, a larger aggregate of cells, such as a tumor embolus, peels more readily from the endothelium than smaller ones. These result may give us insight into the concept of cancer metastatic efficiency. [Preview Abstract] |
Wednesday, March 12, 2008 2:03PM - 2:15PM |
Q16.00013: Implications of Cytoplasmic Streaming for Intracellular Transport and Micro-scale Mixing Jan-Willem van de Meent, Idan Tuval, Wim van Saarloos, Ray Goldstein Found in many large eukaryotic cells, particularly in plants, cytoplasmic streaming is the circulation of their contents driven by fluid entrainment from organelles carried by molecular motors at the cell periphery. Streaming has frequently been conjectured to aid in transport and mixing of molecular species in the cytoplasm, and, by implication, in cellular homeostasis, yet no mechanism quantifying this enhancement has been demonstrated. We solve the flow and its associated advection-diffusion equations for the archetypal `rotational streaming' found in Characean algae, where the cytoplasm streams up and down along helical bands on the surface of cylindrical \emph{internodal} cells. We find that the spiralling flow induces a secondary circulation, reminiscent of Dean vortices found at higher Reynolds numbers, which leads to the formation of a high-flux boundary layer allowing faster uptake and response to changes in external concentration. This effect constitutes a novel example of how high Pecl{\'e}t number flows can facilitate diffusive transport and mixing at the micro-scale. [Preview Abstract] |
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