Bulletin of the American Physical Society
APS March Meeting 2010
Volume 55, Number 2
Monday–Friday, March 15–19, 2010; Portland, Oregon
Session T27: Cellular Biomechanics |
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Sponsoring Units: DBP Chair: Wolfgang Losert, University of Maryland Room: D137 |
Wednesday, March 17, 2010 2:30PM - 2:42PM |
T27.00001: Dynamics of Traction Force Reinforcement in Smooth Muscle Cells Yi-Chia Lin, Corinne Kramer, Christopher Chen, Daniel Reich Mechanical forces influence cell function in various ways. For instance, the force-induced contraction or relaxation of vascular smooth muscle cells (SMCs) is critical to regulating the properties of blood vessels. Here, we study the dynamics of cellular traction forces in SMCs using micro-scale magnetic nanowires together with flexible PDMS micropost arrays. We use dual magnetic tweezers to apply a sinusoidal magnetic torque on nickel nanowires which are internalized by the SMCs. The spatial and temporal responses of the SMCs cultured on the tips of the microposts are recorded by the deflected posts. We observe a global reinforcement of the cells' traction forces upon applying a localized torque via the nanowires. Interestingly, we also find that the contractile response depends on the frequency of the applied stimulation, with a greater percentage of the SMCs showing enhanced reinforcement at lower frequencies. [Preview Abstract] |
Wednesday, March 17, 2010 2:42PM - 2:54PM |
T27.00002: Mechanics of Anisotropic Semiflexible Gels Andrew Missel, Mo Bai, William Klug, Alex Levine We present the results of analytic and numerical investigations into the mechanics of anisotropic semiflexible gels. Previous work has uncovered the existence of an affine/non-affine crossover as a function of the density of cross-links in the semiflexible filament network. The affine regime is characterized by a spatially homogeneous strain field and filament stretching under applied shear strain, while the non-affine regime is characterized by a spatially heterogeneous strain field and filament bending. Previous studies focused on statistically isotropic networks. Here we explore the effect of network anisotropy on the affine/non-affine crossover. We examine elastic energy storage and the geometry of the displacement field in networks having a non-vanishing nematic order parameter under both shearing and stretching deformations. Understanding the impact of filament anisotropy on the affine/non-affine crossover may inform the biophysical study of cellular mechanics where the filamentous networks have locally preferred directions. [Preview Abstract] |
Wednesday, March 17, 2010 2:54PM - 3:06PM |
T27.00003: Intracellular mechanical properties of living cells Ming-Tzo Wei, H. Daniel Ou-Yang In biological systems, internal stresses resulting from molecular motors such as myosin or kinesin, can actively modify cytoskeletal network mechanical properties and quantitatively change the viscoelastic response of network. This paper report a study that uses both passive and active microrheology approaches to measure the inner mechanical properties in living cellular mechanical systems. We examined the mechanical fluctuations in the cells under the conditions where motor activities and cytoskeleton proteins were modulated by chemical treatments. To distinguish the non-thermal nature of the biological activities on the mechanical integrity of the cell interior, results by the passive and active microrheology methods are compared in the context of Fluctuation-Dissipation relation. [Preview Abstract] |
Wednesday, March 17, 2010 3:06PM - 3:18PM |
T27.00004: The size, shape, and dynamics of cellular blebs Keng-Hwee Chiam, Fong Yin Lim, L. Mahadevan Blebs are protrusions of cell membrane driven by intracellular pressure that are commonly seen in many types of cells. Recent studies on cell blebbing have revealed them to be an important mechanism contributing to cell motility. We have developed a quantitative biomechanical model to study how a bleb develops when a portion of the cell membrane detaches from the underlying cortex. From the model, we calculate the minimum cytoplasmic pressure and minimum unsupported membrane length for a bleb to nucleate and grow. We also show how a bleb may travel around the periphery of the cell. The traveling speed is governed by the speed of the pressure changes induced by variations in the cortical contractility. On the other hand, the asymmetry of the shape of the bleb is governed by the healing of actin cortex at the rear end of the bleb. [Preview Abstract] |
Wednesday, March 17, 2010 3:18PM - 3:30PM |
T27.00005: ABSTRACT WITHDRAWN |
Wednesday, March 17, 2010 3:30PM - 3:42PM |
T27.00006: Effect of cell mechanics on instantaneous molecular bond force and measured kinetic parameters Vijay Gupta, Charles Eggleton Receptor-ligand interactions that mediate cellular adhesion are subjected to forces that regulate their dissociation via modulating off-rates. One should be able to determine off-rates from either dissociation force measurements. The correct knowledge of the transient molecular force history is essential for accurate estimation of kinetics parameters through force spectroscopy. Currently, it is assumed that the molecular force is instantaneously equal to the externally applied force. In this work we predict via analytical models and simulation that cell mechanics and hydrodynamics modulates the externally applied force such that the instantaneous bond force is not equivalent. Various mechanical models (solid, elastic, viscoelastic) of cells and microvillus are considered over relevant ranges of loading rates (10$^{2}$-10$^{6 }$pN/s). Specifically it is demonstrated that microvillus extension and tether formation decrease the pulling force imposed on the adhesive bonds leading to a prolonged bond lifetime. It is demonstrated that modulation of molecular force leads to inaccurate estimation of kinetic off-rate even when the cell and microvillus are modeled as solid materials. [Preview Abstract] |
Wednesday, March 17, 2010 3:42PM - 3:54PM |
T27.00007: Probing non-Newtonian cell-matrix interactions with a confocal rheometer Ryan McAllister, Richard Arevalo, Daniel Koch, Jeffrey Urbach, Susette Mueller, Daniel Blair The importance of cell mechanotransduction with the extra cellular matrix (ECM) has become increasingly clear. ECM stiffness affects cell behavior and differentiation, and simultaneously the cell affects the stiffness of the ECM. For example, tumorigenesis and metastatic invasiveness of cancer cells are associated with cell-induced changes in the ECM. Meanwhile, the ECM is a complicated environment where the cells interact with both a variety of proteins and the non-Newtonian network stiffness. In this talk we present preliminary results using a live-cell adapted confocal rheometer to probe the activity and response of human cell-line cells within a type 1 collagen network. [Preview Abstract] |
Wednesday, March 17, 2010 3:54PM - 4:06PM |
T27.00008: Cell migration at the edge of a cliff Wolfgang Losert, Colin McCann, Rael Kopace, Tess Homann, Meghan Driscoll Migrating cells face several decisions about when to move and where to move during chemotaxis, i.e. migration guided by chemical signal.~ Though the behavior of individual cells varies widely, chemotaxis works remarkably reliably for key processes such as wound healing and development, indicating that the process is well controlled. Here we study how chemotaxing cells, specifically the simple model organism \textit{Dictyostelium discoideum} responds mechanically and biochemically when faced with obstacles, in particular cliffs or ridges. The cliffs (and ridges) were fabricated using multiphoton absorption polymerization. As the cells encounter these topographical features, we track their overall motion, cell shape and dynamic changes in shape, as well as the surface adhesion and location of intracellular signals. We find that cells do not fall off the cliff, but extend over the edge with a characteristic motion of the freely suspended part of the cell that appears distinct from the migration characteristics of cells moving along the surface. [Preview Abstract] |
Wednesday, March 17, 2010 4:06PM - 4:18PM |
T27.00009: A Bio-Mechanical Model for Dictyostelium Motility Mathias Buenemann, Herbert Levine, Leonard Sander, Wouter-Jan Rappel The crawling motion of \textsl{Dictyostelium discoideum} consists of a coordinated succession of cell contraction and protrusion. The mechanical forces exerted during this motion have been measured precisely by recent traction force experiments. Based on experimental results, we develop a bio-mechanical model of \textsl{dictyostelium} motility with emphasis of the contraction phase and the adhesive properties of the cell-substratum contact. We assume, that the cell contracts at a constant rate and is bound to the substratum by adhesive bridges which are modeled as elastic springs. These bridges are established at a (spatially uniform) rate while detachment occurs at a spatially varying, load-dependent rate. Using Monte-Carlo simulations, we find that the cell speed depends only weakly on its adhesive properties, in agreement with recent experimental results. Varying the parameters that characterize the adhesive properties and contraction of the cell, we are able to make testable predictions, e.g. for mutants with deficient adhesiveness or an impaired contractile machinery. As an extension of our model, we also included the substrate stiffness. We find substratum deformations and traction stresses that are quantitatively in good agreement with experimental data. [Preview Abstract] |
Wednesday, March 17, 2010 4:18PM - 4:30PM |
T27.00010: Feeling for Cells with Light: Illuminating the Role of Biomechanics for Tumor Progession Josef A. Kas, Anatol Fritsch, Franziska Wetzel, Tobias Kiessling, Kenechukwu D. Nnetu, Mareike Zink Light has been used to observe cells since Leeuwenhoek's times; however, we use the forces caused by light described by Maxwell's surface tensor to feel for the cellular cytoskeleton. The cytoskeleton, a compound of highly dynamic polymers and active nano-elements inside biological cells, is responsible for a cell's stability and organization. The optical stretcher exploits the nonlinear, thus amplified response of a cell's mechanical strength to small changes between different cytoskeletal proteomic compositions as a high precision cell marker that uniquely characterizes different cell types. Consequentially, the optical stretcher detects tumors and their stages with accuracy unparalleled by molecular biology. As implied by developmental biology the compartmentalization of cells and the epithelial-mesenchymal transition that allows cells to overcome compartmental boundaries strongly depend on cell stiffness and adhesiveness. Consequentially, biomechanical changes are key when metastatic cells become able to leave the boundaries of the primary tumor. [Preview Abstract] |
Wednesday, March 17, 2010 4:30PM - 4:42PM |
T27.00011: Forward ray tracing method for simulating transient cell optical deformation Ihab Sraj, David Marr, Charles Eggleton The mechanical deformation of biological cells using optical forces may be used to study the cellular properties and identify diseased cells. Optical stretchers generally require minimal direct contact compared to other experimental techniques (micro-pipette aspiration, atomic force microscopy). A pseudo steady-state high-throughput optical stretcher can be implemented where anisotropic forces stretch red blood cells (RBC) ghosts within rapidly flowing microfluidic environments. This approach employs a single linear optical trap instead of a focused spot using an inexpensive diode laser bar. In this work we simulate an optical stretcher based on a single light source. We model the RBC ghost deformation induced by this stretcher as a function of applied optical trap power using the immersed boundary method (IBM) coupled with ray-optics. Cells are considered as 3D elastic capsules immersed in fluid exposed to a light source. The optical forces distribution is first calculated using a forward ray tracing method on the cell surface for different geometrical shapes (spheres, ellipsoids or even biconcave). Then the transient deformation of RBC ghosts due to the applied optical forces was simulated. The simulation results are used to develop a method for calculating cell stiffness properties based on static deformation. [Preview Abstract] |
Wednesday, March 17, 2010 4:42PM - 4:54PM |
T27.00012: Polydispersity in semiflexible networks: Implications for mechanics of the cytoskeleton Mo Bai, Andrew Missel, William Klug, Alex Levine Semiflexible networks admit a nonaffine-to-affine (A/NA) crossover -- an abrupt transition with increasing crosslink density from a soft, bending-dominated nonaffine network to a stiffer affine network in which elastic energy is stored primarily in stretching. Studies have shown that there is a single control parameter determining the network's affinity: the ratio of the length of a constituent filament to the so- called nonaffinity length, which is a function of both the mechanical moduli of the filaments and the density of the network. This result suggests important questions regarding the A/NA crossover in heterogeneous networks. We extend the previous analysis to two classes of heterogeneous networks by considering: (i) length polydispersity, and (ii) mechanical heterogeneity, using networks composed of stiffer and more compliant filaments. Both systems have direct implications to the mechanics of living cells. We show that the addition of a small fraction of longer and stiffer filaments to a nonaffine network leads to significant increases in its elastic moduli even when the stiffer filaments are at such a low density so as to not form a stress bearing network. We present a new A/NA phase diagram for networks composed of filaments of two lengths and present results for the mechanics of networks having a continuous distribution of filament lengths, similar to those found in in vitro F-actin experiments. [Preview Abstract] |
Wednesday, March 17, 2010 4:54PM - 5:06PM |
T27.00013: Effects of motor-induced stresses and pre-stress on the elasticity of semiflexible cytoskeletal networks William Klug, Andrew Missel, Mo Bai, Alex Levine The control of the elasticity of cytoskeletal networks appears to rely on the combination of a nonequilibrium state of internal stress generated by molecular motors and the inherently nonlinear stress strain response of the constituent filaments. F-actin is strongly strain hardening under tension so that tensile stresses applied by myosin motors can stiffen the network dramatically. Experiments by Mizuno, Schmidt, and collaborators have shown that the action of these molecular motors can generate hundred-fold increases in the network's modulus. In this talk we present the results of new theoretical and numerical investigations of this phenomenon. Using a newly-developed coarse-grained elastic model of the individual filaments that incorporates a linear bending and a nonlinear stretching response consistent with wormlike chain behavior, we examine the effect of the action of myosin-like molecular motors on the material's elastic constants. The motors generate internal loads due to the application of contractile force pairs to adjacent filaments. Using this model we quantitatively explore the dependence of the nonequilibrium stiffening of the network as a function of the density of active motors. Moreover, we study the effect of quenched pre-stresses on network elastic response. [Preview Abstract] |
Wednesday, March 17, 2010 5:06PM - 5:18PM |
T27.00014: Insights into the Cell Shape Dynamics of Migrating \textit{Dictyostelium discoideum} Meghan Driscoll, Tess Homan, Colin McCann, Carole Parent, John Fourkas, Wolfgang Losert Dynamic cell shape is a highly visible manifestation of the interaction between the internal biochemical state of a cell and its external environment. We analyzed the dynamic cell shape of migrating cells using the model system Dictyostelium discoideum. Applying a snake algorithm to experimental movies, we extracted cell boundaries in each frame and followed local boundary motion over long time intervals. Using a local motion measure that corresponds to protrusive/retractive activity, we found that protrusions are intermittent and zig-zag, whereas retractions are more sustained and straight. Correlations of this local motion measure reveal that protrusions appear more localized than retractions. Using a local shape measure, curvature, we also found that small peaks in boundary curvature tend to originate at the front of cells and propagate backwards. We will review the possible cytoskeletal origin of these mechanical waves. [Preview Abstract] |
Wednesday, March 17, 2010 5:18PM - 5:30PM |
T27.00015: Spectroscopic Studies of High Pressure Effects on Single Erythrocytes Silki Arora, Sang Hoon Park, Lawrence Ayong, Debopam Chakrabarti, Alfons Schulte Pressure is an important thermodynamic variable that affects the metabolism of living cells and the rate of a biochemical reaction. We investigate morphological and functional changes in single erythrocytes as a function of pressure. Optical absorption spectroscopy is used to measure the hemoglobin oxygenation in red blood cells. With increasing pressure (0.1 to 200 MPa) the maximum of the Soret absorption band shifts to longer wavelengths by about 0.8 nm (45 cm$^{-1})$. We attribute this shift to a conformational contribution. However, the small peakshift is indicating that the hemoglobin stays oxygenated. Transient absorption spectroscopy is employed to probe pressure effects on the ligand binding kinetics of hemoglobin. Results will be compared with the kinetics in myoglobin at variable pressure and temperature. [Preview Abstract] |
Wednesday, March 17, 2010 5:30PM - 5:42PM |
T27.00016: Measurement of spatio-temporal transport in live cells Ru Wang, Zhuo Wang, Larry Millet, Martha U. Gillette, Gabriel Popescu The live cell is a highly dynamical system with complicated biophysical and biochemical processes taking place at diverse spatiotemporal scales. Though it is well known that microtubules and actin filaments play important roles in intracellular transport, their dynamic behavior is not entirely understood. We propose a unified approach to studying transport in live cells. We used Spatial Light Interference Microscopy, a quantitative phase imaging method developed in our laboratory, to extract cell mass distributions over broad spatiotemporal scales. The dispersion relations for this transport dynamics, i.e. frequency bandwidth vs. spatial frequencies, reveal deterministic mass transport at large spatial scales (w$\sim $q) and diffusive transport at small spatial scales (w$\sim $q\^{}2). At submicron scales, we observed a w$\sim $q\^{}3 behavior, which indicates whip-like movements of protein filaments. Further control experiments where both the microtubule and actin polymerization were blocked suggests that essentially actin governs the long spatial scales behavior and microtubules the short scales. This label-free method enables us to access different components of cell dynamics and quantify diffusion coefficients and speed of motor proteins. [Preview Abstract] |
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