Bulletin of the American Physical Society
APS March Meeting 2011
Volume 56, Number 1
Monday–Friday, March 21–25, 2011; Dallas, Texas
Session V39: Cellular Biomechanics |
Hide Abstracts |
Sponsoring Units: DBP Chair: Helim Aranda-Espinoza, University of Maryland Room: A124/127 |
Thursday, March 24, 2011 8:00AM - 8:12AM |
V39.00001: Three-dimensional traction force distribution in migrating amoeboid cells Begona Alvarez, Juan C. del Alamo, Rudolf Meili, Baldomero Alonso-Latorre, Richard A. Firtel, Juan C. Lasheras We have studied the 3D traction forces exerted by migrating \textit{Dictyostelium} cells moving over flat elastic substrates. For that purpose, we have developed a method to calculate both vertical and tangential cell traction forces from measurements of 3D substrate deformation, based on the solution of the elastostatic equation for a linearly elastic medium. 3D substrate deformation is measured by applying correlation techniques to a volume of substrate containing fluorescent markers. We have performed experiments for wild-type (WT) and mutant cell lines with crosslinking defects to study how cytoskeletal organization affects the overall distribution of traction forces. We find that cells push the substrate downwards near their center and pull upwards at their periphery with forces of comparable magnitude. Our initial findings show that the effect of the crosslinking mutations on the tangential forces do not necessarily predict the effect on the vertical forces. For instance, myosin II-null cells show a significant reduction of the front-back organization of the tangential traction forces, while the distribution of vertical forces basically remains unaffected. [Preview Abstract] |
Thursday, March 24, 2011 8:12AM - 8:24AM |
V39.00002: The Physics Of Cell Crawling In Elastic Media Elnaz Baum-Snow, Charles Wolgemuth Understanding the motion of cells through deformable media, such as the extra-cellular matrix (ECM), is important for understanding many biological processes, such as cancer metastasis, wound healing, and organismal development. We propose a model to understand the cells' movements through ECM, described by an elastic medium. The deformations and the stress tensor are then calculated for different values of Young's modulus and Poisson's ratio. The results are then compared to the values measured experimentally. [Preview Abstract] |
Thursday, March 24, 2011 8:24AM - 8:36AM |
V39.00003: How Deep Cells Feel Amnon Buxboim, Edward C. Eckels, Dennis E. Discher Lacking eyes to see and ears to hear, cells can still sense their microenvironment by physically touching and deforming, thus sensing not only their immediate surroundings but also feeling beyond the cell-matrix interface. To elucidate how deeply cells feel we cultured mesenchymal stem cells on gels-made microfilms with controlled elasticity (E) and thickness (h). After 36hrs in culture cells spread area was smaller on thick and on soft than on thin and on stiff films, respectively, and correlated with nuclei morphology. Transition in spread area was obtained at $<$5 microns gel thickness. Transcription levels of Lamin-A predominantly decreased with E and in a similar fashion to Lamin-A expression levels increased with h. RNA levels of histones and of chromatin-remodeling enzymes were similar for stiff gels and for soft but thin films but suppression of cell contractility resulted in transcriptional profiles that were uncorrelated with matrix-emerging cues. We conclude that cells actively sense up to 20 microns into soft, adipose-like matrix. Cellular response to E and h includes cytoskeletal reorganization, NE remodeling with evidence of coupling between matrix-emerging signals and regulation of gene expression [Preview Abstract] |
Thursday, March 24, 2011 8:36AM - 8:48AM |
V39.00004: Delineating cell-matrix interaction at high resolution Shang You Tee, John Crocker, Paul Janmey It is increasingly evident that mechanic cues affect a wide variety of cells and can sometimes override biochemical cues to control cell division, cell death and even specify stem cell differentiation lineage. To understand how cells interact physically with their surrounding matrix, it is imperative to investigate the spatiotemporal distribution of forces and molecular players as cells undergo contractile activity. We examine human mesenchymal stem cell contractility at high temporal and spatial resolution on soft and hard substrates. [Preview Abstract] |
Thursday, March 24, 2011 8:48AM - 9:00AM |
V39.00005: How substrate rigidity regulates the cellular motility Alireza Sarvestani Mechanical stiffness of bio-adhesive substrates has been recognized as a major regulator of cell motility. We present a simple physical model to study the crawling locomotion of a contractile cell on a soft elastic substrate. The mechanism of rigidity sensing is accounted for using Schwarz's two spring model (Schwarz et al. (2006) BioSystems 83, 225-232). The predicted dependency between the speed of motility and substrate stiffness is qualitatively consistent with experimental observations. The model demonstrates that the rigidity dependent motility of cells is rooted in the regulation of actomyosin contractile forces by substrate deformation at each anchorage point. On stiffer substrates, the traction forces required for cell translocation acquire larger magnitude but show weaker asymmetry which leads to slower cell motility. On very soft substrates, the model predicts a biphasic relationship between the substrate rigidity and the speed of locomotion, over a narrow stiffness range, which has been observed experimentally for some cell types. [Preview Abstract] |
Thursday, March 24, 2011 9:00AM - 9:12AM |
V39.00006: Local nano-mechanical properties in cancer metastasis Lyndon Bastatas, Raul Martinez-Zaguilan, Souad Sennoune, Soyeun Park We investigated whether the local nano-mechanical properties of cells can represent metastatic potential using the Atomic Force Microscope. As models, we used the lowly (LNCaP) and highly (CL1) metastatic prostate cancer cells. By varying the applied forces, we determined the heterogeneity in the local elastic properties of cells in the vertical direction. We also obtained the 2D array of the force-distance curves over the entire region of cells to investigate the lateral heterogeneity of local elastic moduli. By analyzing the force-distance curves using the Hertz and the advanced models, we delineated the 2D maps of elastic moduli and adhesiveness of cells. We found that the CL1 is more heterogeneous in the local elastic moduli compared to LNCaP. We also found that the CL1 adheres much better on the substrates than the LNCaP. The enhanced adhesion generates the tensional force and thus results in higher elastic moduli. We conclude that there is an optimal range of elastic moduli to make cells actively elicit the directional movements, leading to the enhance metastasis. We will discuss our results correlated with our intercellular calcium transit. [Preview Abstract] |
Thursday, March 24, 2011 9:12AM - 9:24AM |
V39.00007: Cell Shape Dynamics: From Waves to Migration Meghan Driscoll, Colin McCann, Rael Kopace, Tess Homan, John Fourkas, Carole Parent, Wolfgang Losert We analyzed the dynamic shape of migrating Dictyostelium discoideum cells. We found that regions of high boundary curvature propagate from the front to the back of cells in an organized fashion. These waves of high curvature are stabilized by surface contact, and so, at the sides of cells, are stationary relative to the surface. The initiation of curvature waves, though, which usually occurs at the front of cells, is associated with protrusive motion. The protrusion location shifts rapidly in a ballistic manner at speeds nearly double that of cellular migration. To examine curvature waves in the absence of surface contact, we guided cells to extend over the edge of micro-cliffs. The curvature wave speed of cells extended over a cliff was triple the wave speed of cells migrating on a surface, which is consistent with the higher wave speeds observed near the non-adherent leading edge of cells. [Preview Abstract] |
Thursday, March 24, 2011 9:24AM - 9:36AM |
V39.00008: Self-organized cell motility XinXin Du, Konstantin Doubrovinski Cell migration plays a key role in a wide range of biological phenomena, such as morphogenesis, chemotaxis, and wound healing. Cell locomotion relies on the cytoskeleton, a meshwork of filamentous proteins, intrinsically out of thermodynamic equilibrium and cross-linked by molecular motors, proteins that turn chemical energy into mechanical work. In the course of locomotion, cells remain polarized, i.e. they retain a single direction of motion in the absence of external cues. Traditionally, polarization has been attributed to intracellular signaling. However, recent experiments show that polarization may be a consequence of self-organized cytoskeletal dynamics. Our aim is to elucidate the mechanisms by which persistent unidirectional locomotion may arise through simple mechanical interactions of the cytoskeletal proteins. To this end, we develop a simple physical description of cytoskeletal dynamics. We find that the proposed description accounts for a range of phenomena associated with cell motility, including spontaneous polarization, persistent unidirectional motion, and the co-existence of motile and non-motile states. [Preview Abstract] |
Thursday, March 24, 2011 9:36AM - 9:48AM |
V39.00009: Differentiation and Behavior of Dental Pulp Stem Cells in Hydrogel Scaffolds of Various Stiffnesses Divya Bhatnagar, Vladimir Jurukovski, Miriam Rafailovich, Marcia Simon Dental Pulp Stem Cells (DPSCs) are known to differentiate in bone, dentine, or nerve tissue through different environment signals. This work investigates whether differentiation could occur in the absence of chemical induction and through mechanical stimuli only. For this study, we chose enzymatically cross-linked gelatin hydrogels as our substrates. Rheological studies carried out by oscillatory shear rheometry indicated that the modulus of the hardest hydrogel was of the order of 8kPa where as the medium and the softest hydrogel had modulus of the order of 1kPa and 100Pa respectively. DPSC were then plated on all three substrates and cultured with and without dexamethasone induction media. After 21 days of incubation, SEM analysis indicated that the cells cultured in the induction media produced biomineralized deposits on hard, medium as well as soft hydrogels. On the other hand, the cells cultured without the induction media also produced large amounts of biomineralized deposits.The modulus of the cells was also measured using AFM. En mass cell migration was also studied to determine the average velocity of migration of DPSCs. We also investigated whether stem cells that are induced to differentiate by their scaffold environment would continue to differentiate and biomineralize when removed from the inducing scaffold. [Preview Abstract] |
Thursday, March 24, 2011 9:48AM - 10:00AM |
V39.00010: Model of myosin recruitment to the cell equator for cytokinesis: feedback mechanisms and dynamical regimes Alexander Veksler, Dimitrios Vavylonis The formation and constriction of the contractile ring during cytokinesis, the final step of cell division, depends on the recruitment of motor protein myosin to the cell's equatorial region. During animal cell cytokinesis, cortical myosin filaments (MF) disassemble at the flanking regions and concentrate in the equator [1]. This recruitment depends on myosin motor activity and the Rho proteins that regulate MF assembly and disassembly. Central spindle and astral microtubules help establish a spatial pattern of differential Rho activity [2]. We propose a reaction-diffusion model for the dynamics of MF recruitment to the equatorial region. In the model, the central spindle and mechanical stress [3] promote self-reinforcing MF assembly. Negative feedback is introduced by MF-induced recruitment of inhibitor myosin phosphatase. Our model yields various dynamical regimes and explains both the recruitment of MF to the cleavage furrow and the observed damped MF oscillations in the flanking regions [1], as well as steady MF assembly [4]. Space and time parameters of MF oscillations are calculated. We predict oscillatory relaxation of cortical MF upon removal of locally-applied external stress. [1] Zhou {\&} Wang, Mol. Biol. Cell \textbf{19}:318 (2008); [2] Murthy {\&} Wadsworth, J. Cell Sci. \textbf{121}:2350 (2008); [3] Ren et al., Curr. Biol. \textbf{19}:1421 (2009); [4] Vale et al., J. Cell Biol. \textbf{186}:727 (2009) [Preview Abstract] |
Thursday, March 24, 2011 10:00AM - 10:12AM |
V39.00011: Biomechanics and dynamics of red blood cells probed by optical tweezers and digital holographic microscopy Nelson Cardenas, Pattrick Thomas, Lingfeng Yu, Samarendra Mohanty Red blood cells (RBC), with their unique viscoelastic properties, can undergo large deformations during interaction with fluid flow and migration through narrow capillaries. Both local and overall viscoelastic property is important for cellular function and change in these properties indicate diseased condition. Though biomechanics of the cells have been studied using variety of physical techniques (AFM, optically-trapped anchoring beads and microcapilary aspiration) in force regime $>$ 10pN, little is studied at low force regime $<$1pN. Such perturbations are not only hard to exercise on the cell membrane, but quantification of such deformations becomes extremely difficult. By application of low power optical tweezers directly on cell membrane, we could locally perturb discotic RBC along the axial direction, which was monitored dynamically by digital holographic microscopy-a real time, wide-field imaging method having nm axial resolution. The viscoelastic property of the RBC at low force regime was found to be significantly different from that of high-force regime. The results were found to be in good agreement with the simulation results obtained using finite element model of the axially-stretched RBC. The simulations and results of viscoelestic measurements will be presented. [Preview Abstract] |
Thursday, March 24, 2011 10:12AM - 10:24AM |
V39.00012: Effect of Surface Adhesion on Individual and Collective Migration Wolfgang Losert, Colin McCann, Erin Rericha, Carole Parent Cell-surface adhesion plays a critical role in amoeboid cell motion by supplying the traction allowing a cell to move itself forward.~ The amoeba Dictyostelium discoideum, a model system for individual and collective cell migration, naturally exhibits both cell-substrate and cell-cell adhesion during the aggregation process.~ We used both high- and low-magnification time-lapse microscopy to investigate the individual and collective migration of D. discoideum on substrates of varying adhesiveness, as well as on interfaces between surfaces.~ We find that surface adhesion can affect both individual cell migration as well as the behavior of cell groups.~ At the population scale, non-ideal surfaces slow down the initiation of aggregation and change the aggregation dynamics. At the scale of single cells, we measure both adhesion ability as well as the area of contact between cells and surface for individual cells and cells that are part of groups.~ We find that comparable forces are needed to pull cells off all surfaces, indicating that surface adhesion is actively regulated by migrating cells. [Preview Abstract] |
Thursday, March 24, 2011 10:24AM - 10:36AM |
V39.00013: Importance of spectrin network reorganization in computer simulations of RBC shapes Ulf Schiller, Tony Ladd The shape of red blood cells (RBCs) has been the subject of intensive investigations in both experiments and theoretical models. Various computational models for RBCs have also been developed. However, a rigorous quantitative comparison of the observed shapes is still lacking. We have developed a flexible model that allows to study the influence of the various contributions to the membrane stress and their relevance for RBC shape. Our model reveals that a pure curvature model does not fully explain the experimentally observed discocyte shapes. We demonstrate that the in-plane stresses of the spectrin network have a crucial effect on the cell shapes and their transitions, and that the dynamic relaxation of the stresses due to spectrin reorganization is important. We present an extended model that incorporates the effects of dynamic spectrin remodeling and study their role on the dynamics of RBC shapes. [Preview Abstract] |
Thursday, March 24, 2011 10:36AM - 10:48AM |
V39.00014: The contribution of cytoskeleton networks to stretch is strain dependent Kenechukwu David Nnetu, Tobias Kie{\ss}ling, Roland Stange, Josef K\"as The interaction between the cytoskeleton filaments in a cell provides it with mechanical stability and enables it to remodel its shape. The rheological response of cells has been characterized either as viscoelastic or soft-glassy which neglects the molecular origin of cell response. In this work, by using a large amount of cells ($>$10,000 in total) exceeding previous statistics by a decade, we link observed cell response to its molecular origin by showing that actin and microtubule networks maintain the mechanical integrity of cells in a strain dependent manner. While the actin network solely regulated cell deformation at small strain, the microtubule network was responsible for cell relaxation. At large strain, actin and microtubule networks dominated cell response with microtubules having a bipolar effect on cells upon stabilization. This effect could explain the relapse of some cancer after chemotherapy treatment using Taxol thus providing a bridge between soft condense matter physics and systems biology. [Preview Abstract] |
Thursday, March 24, 2011 10:48AM - 11:00AM |
V39.00015: Magnetic Carbon nanoparticles enabled efficient photothermal alteration of mammalian cells L. Gu, V. Vardarajan, A. Kanneganti, A. Koymen, S.K. Mohanty While cw near-infrared (NIR) laser beams have been finding widespread application in photothermal therapy of cancer and pulsed NIR laser microbeams are recently being used for optoporation of exogeneous impermeable materials into cells. Since, carbon nanomaterials are very good in photothermal conversion, we utilized carbon nanoparticles (CNP) doped with Fe, so that they can be localized in a defined area by two fold selectivity, (i) external magnetic field for retention of the CNP in targeted area and (ii) surface functionalization for binding the targeted cells. Here, we report efficient photothermal therapy as well as poration of cells using magnetic CNPs with very low power continuous wave laser beam. Localization of CNPs on cell membrane under application of magnetic field was confirmed by scanning electron microscopy. At different power levels, cells could be damaged or microinjected with fluorescence protein-encoding plasmids or impermeable dyes. Monte Carlo simulation showed that the dose of NIR laser beam is sufficient to elicit response for magnetic CNP based photothermal treatment at significant depth. The results of our study suggest that magnetic CNP based photothermal alteration is a viable approach to remotely guide treatments offering high efficiency with significantly reduced cytotoxicity. [Preview Abstract] |
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