Bulletin of the American Physical Society
APS March Meeting 2010
Volume 55, Number 2
Monday–Friday, March 15–19, 2010; Portland, Oregon
Session Q11: Self-organization in Biological Cells and tissue II |
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Sponsoring Units: DBP Chair: Tim Newman, Arizona State Room: A107-A109 |
Wednesday, March 17, 2010 11:15AM - 11:27AM |
Q11.00001: Modeling cell-cycle synchronization during embryogenesis in Xenopus laevis R. Scott McIsaac, K.C. Huang, Anirvan Sengupta, Ned Wingreen A widely conserved aspect of embryogenesis is the ability to synchronize nuclear divisions post-fertilization. How is synchronization achieved? Given a typical protein diffusion constant of $10 \frac{\mu m^2}{sec}$, and an embryo length of $\approx 1mm$, it would take diffusion many hours to propagate a signal across the embryo. Therefore, synchrony cannot be attained by diffusion alone. We hypothesize that known autocatalytic reactions of cell-cycle components make the embryo an ``active medium'' in which waves propagate much faster than diffusion, enforcing synchrony. We report on robust spatial synchronization of components of the core cell cycle circuit based on a mathematical model previously determined by in vitro experiments. In vivo, synchronized divisions are preceded by a rapid calcium wave that sweeps across the embryo. Experimental evidence supports the hypothesis that increases in transient calcium levels lead to derepression of a negative feedback loop, allowing cell divisions to start. Preliminary results indicate a novel relationship between the speed of the initial calcium wave and the ability to achieve synchronous cell divisions. [Preview Abstract] |
Wednesday, March 17, 2010 11:27AM - 11:39AM |
Q11.00002: Probing the mechanics of pulsed contractions in embryonic epithelial cells Xiaoyan Ma, M. Shane Hutson During the dorsal closure stage of fruit fly embryogenesis, epithelial cells in the amnioserosa undergo multiple pulsed contractions of their apical surfaces. These pulsed contractions are important for proper dorsal closure and models have been proposed for the force feedbacks that lead to pulsed contractions; however, the correlation between the observed contractions and the hypothesized forces has not yet been experimentally investigated. We performed laser hole-drilling to probe how the cellular mechanics change during a contraction cycle. We find that cell-center wounds expand faster and farther when a cell is in the expanded half of its cycle. In contrast, cell-edge wounds expand faster and farther when the edge is in the process of contracting. These results imply different roles for cortical tensions along the lateral and apical cell surfaces during the contraction cycle. [Preview Abstract] |
Wednesday, March 17, 2010 11:39AM - 11:51AM |
Q11.00003: Beating of early embryonic cardiomyocytes: definitive modulation and possible induction by matrix elasticity Stephanie Majkut, Christine Krieger, Dennis Discher Previous studies on the effects of matrix elasticity on chicken cardiomyocyte beating physiology have focused on 10 day embryo cells[1]. In this study we investigated the effects of matrix elasticity on cardiomyocyte development at earlier stages. At these stages, it is known that matrix proteins like collagen and fibronectin (FN) are expressed, and there is definite differentiation. Cardiomyocytes were isolated from 2-4 day chicken embryos, cultured on collagen- or FN-coated PA gels of varying stiffness, and observed for spontaneous beating and morphology. 4 day embryo cells adhered to both matrix ligands, although cells cultured on FN had more frequent and pronounced protrusions than those cultured on collagen. After 18 hours in culture, cardiomyocyte beating magnitude was larger on softer 1 kPa gels than on stiffer 34 kPa gels. Thus, early embryonic cells showed matrix-dependent morphology and differentiated function. Beating heart tubes are seen in embryos as early as 2 days, while there are no beating cells at 1 day, so the physical system used in this study seems ideal for assessing microenvironment effects on early embryonic development of heart cells. [1] A. Engler, et al. \textbf{\textit{Journal of Cell Science}} 121: 3794-3802 (2008). [Preview Abstract] |
Wednesday, March 17, 2010 11:51AM - 12:27PM |
Q11.00004: Epithelial self-organization in fruit fly embryogenesis Invited Speaker: During fruit fly embryogenesis, there are several morphogenetic events in which sheets of epithelial cells expand, contract and bend due to coordinated intra- and intercellular forces. This tissue-level reshaping is accompanied by changes in the shape and arrangement of individual cells -- changes that can be measured quantitatively and dynamically using modern live-cell imaging techniques. Such data sets represent rich targets for computational modeling of self-organization; however, reproducing the observed cell- and tissue-level reshaping is not enough. The inverse problem of using cell shape changes to determine cell-level forces is ill-posed -- yielding non-unique solutions that cannot discriminate between active changes in cell shape and passive deformation. These non-unique solutions can be tested experimentally using \textit{in vivo} laser-microsurgery -- i.e., cutting a targeted region of an epithelium and carefully tracking the temporal and spatial dependence of the subsequent strain relaxation. This technique uses a variety of incisions (hole, line or closed curve) to probe different aspects of epithelial mechanics: the local mesoscopic strain; the distribution of intracellular forces; changes in the cell-level power-law rheology; and the question of active versus passive deformation. I will discuss my group's work using laser-microsurgery to investigate two morphogenetic events in fruit fly embryogenesis: germband retraction and dorsal closure. In both cases, we find a substantial active mechanical role for the amnioserosa -- an epithelium that undergoes apoptosis near the end of embryogenesis and makes no part of the fly larva -- in reshaping an adjacent epithelium that becomes the larval epidermis. In these examples, self-organization of the fly embryo relies not only on self-organization of individual tissues, but also on the mechanical interactions between tissues. [Preview Abstract] |
Wednesday, March 17, 2010 12:27PM - 12:39PM |
Q11.00005: How do mechanical interactions generate surface tension in tissues? Lisa Manning, Ramsey Foty, Eva-Maria Schoetz Many biological tissues behave like viscous fluids on long timescales and posses a macroscopic, measurable surface tension. This surface tension correlates strongly with tissue type and successfully explains cell sorting of embryonic tissues. Both the differential adhesion hypothesis (DAH), which postulates that surface tension is proportional to the expression levels of adhesion molecules, and the differential interfacial tension hypothesis (DITH), which suggests that surface tension is generated by differences in the contractility of individual cell interfaces, have been used to explain experimental data. We have developed a minimal model that considers cell adhesion and cortical tension, incorporating ideas from both the DAH and the DITH. This model can successfully explain the available experimental data and differs from previous analyses because it considers the feedback between mechanical energy and geometry and makes novel predictions about the shapes of cells on the surface of an aggregate, which we verify experimentally. Combining numerical simulations with analytic results, we predict how tissue surface tension varies as the ratio between adhesion and the cortical tension is altered. We find that surface tension increases with adhesion for a large range of parameters, but that there is a regime in which the cortical tension is important. [Preview Abstract] |
Wednesday, March 17, 2010 12:39PM - 12:51PM |
Q11.00006: Long distance substrate deformation patterns guide collective cell migration Thomas Angelini, Edouard Hannezo, Xavier Trepat, Jeffrey Fredberg, David Weitz Most eukaryotic cell types can sense and respond to the mechanical properties of their surroundings, influencing embryo development, tissue function, and wound healing. These are multi-cellular behaviors, yet most detailed knowledge of mechano-sensitivity comes from single cell studies, and very little is known about mechanical communication between cells in large multi-cellular systems. In this talk we will present studies of collective cell motion on a deformable surface, allowing us to probe substrate mediated cell-cell interactions. We show that the cell layer exerts long-distance, multi-cellular forces that generate large-scale deformation patterns in the substrate below. Surprisingly, cell groups move over the deformed surface in collective swirls, and as the substrate deformation patterns grow, so do the swirls of migrating cells. The substrate deformation patterns guide cell motion, as changes in substrate deformations precede changes in migration velocity. Thus, multi-cellular substrate deformation patterns are a type of long-distance mechanical communication between cells that controls their collective migration. [Preview Abstract] |
Wednesday, March 17, 2010 12:51PM - 1:03PM |
Q11.00007: A possible role for chemotaxis in primitive streak formation Sebastian A. Sandersius, Cornelis J. Weijer, Timothy J. Newman One of the fundamental problems in modern biology is to understand the transformation of a fertilized egg to an adult organism. A key stage of this developmental process is gastrulation, in which cell germ layers are defined, and the basic three-dimensional body plan of the organism is established. Presented here is a model used to investigate the collective cell movement which is observed at the onset of gastrulation in the Chick embryo. In the avian embryo, gastrulation is initiated by a cadre of cells moving coherently, bisecting the embryo, thereby forming a structure known as the primitive streak. The mechanisms underlying primitive streak formation are the subject of recent experimental controversy. One hypothesis is that coherent cell motion is driven by chemotactic response to long-range signaling gradients. We will present results from large-scale computer simulations testing this hypothesis. In particular, we perform simulations using the Subcellular Element Model (SEM). Within the model framework, a single cell is represented by a collection of visco-elastically interacting elements. Dynamic interactions of elements are motivated, as coarse-grained representations, of the actively remodeling cell cytoskeleton. We have found that, in addition to chemotaxis, active cell migration is crucial for ``fluidizing" the tissue thereby allowing large-scale coherent cell movement. [Preview Abstract] |
Wednesday, March 17, 2010 1:03PM - 1:39PM |
Q11.00008: Tissue Motion and Assembly During Early Cardiovascular Morphogenesis Invited Speaker: Conventional dogma in the field of cardiovascular developmental biology suggests that cardiac precursor cells migrate to the embryonic midline to form a tubular heart. These progenitors are believed to move relative to their extracellular matrix (ECM); responding to stimulatory and inhibitory cues in their environment. The tubular heart that is formed by 30 hours post fertilization is comprised of two concentric layers: the muscular myocardium and the endothelial-like endocardium, which are separated by a thick layer of ECM believed to be secreted predominantly by the myocardial cells. Here we describe the origin and motility of fluorescently tagged endocardial precursors in transgenic (Tie1-YFP) quail embryos (R. Lansford, Caltech) using epifluorescence time-lapse imaging. To visualize the environment of migrating endocardial progenitors, we labeled two ECM components, fibronectin and fibrillin-2, via in vivo microinjection of fluorochrome-conjugated monoclonal antibodies. Dynamic imaging was performed at stages encompassing tubular heart assembly and early looping. We established the motion of endocardial precursor cells and presumptive cardiac ECM fibrils using both object tracking and particle image velocimetry (image cross correlation). We determined the relative importance of directed cell autonomous motility versus passive tissue movements in endocardial morphogenesis. The data show presumptive endocardial cells and cardiac ECM fibrils are swept passively into the anterior and posterior poles of the elongating tubular heart. These quantitative data indicate the contribution of cell autonomous motility displayed by endocardial precursors is limited. Thus, tissue motion drives most of the cell displacements during endocardial morphogenesis. [Preview Abstract] |
Wednesday, March 17, 2010 1:39PM - 1:51PM |
Q11.00009: Macroscopic dynamics of biological cells interacting via chemotaxis and direct contact Pavel Lushnikov A connection is established between discrete stochastic model describing microscopic motion of fluctuating cells, and macroscopic equations describing dynamics of cellular density. Cells move towards chemical gradient (process called chemotaxis) with their shapes randomly fluctuating. Nonlinear diffusion equation is derived from microscopic dynamics in dimensions one and two using excluded volume approach. Nonlinear diffusion coefficient depends on cellular volume fraction and it is demonstrated to prevent collapse of cellular density. A very good agreement is shown between Monte Carlo simulations of the microscopic Cellular Potts Model and numerical solutions of the macroscopic equations for relatively large cellular volume fractions about 0.3. Combination of microscopic and macroscopic models were used to simulate growth of structures similar to early vascular networks. [Preview Abstract] |
Wednesday, March 17, 2010 1:51PM - 2:03PM |
Q11.00010: Morphometry and structure of natural random tilings Primoz Ziherl, Ana Hocevar, Samir El Shawish To better understand the observed universality of their structure, we analyze the morphometry of a sizable set of living and inanimate planar cellular partitions including patterns seen in animal and plant tissues as well as in magnetic froths and geological formations. We characterize them by the distributions of polygon reduced area, a scale-free measure of the roundedness of polygons. The distributions extracted from experimental images are all fairly sharp and seem to belong to the same family. By comparing the frequencies of the polygon classes, we map the samples onto maximal-entropy model tilings of equal-area, equal-perimeter polygons [1]. We argue that the random two-dimensional patterns studied can be parametrized solely by their median reduced areas. The biological, mechanical, thermodynamical, or other processes which mold the cellular partitions are essential as generators of a certain preferred tile reduced area but beyond that, the structure of a tiling seems to be independent of its material existence. \break [1] A. Hocevar and P. Ziherl, Degenerate polygonal tilings in simple animal tissues, Phys. Rev. E {\bf 80}, 011904 (2009). [Preview Abstract] |
Wednesday, March 17, 2010 2:03PM - 2:15PM |
Q11.00011: Probing the Forces of Germband Retraction with Laser-Microsurgery Holley Lynch, Brett Rosenthal, Elliott Kim, Robert Gish, M. Shane Hutson Germband retraction is a stage of fruit fly embryogenesis that involves the coordinated movement of two tissues: the germband (GB), which uncurls while its cells elongate, and the amnioserosa (AS), whose cells shorten their long axis. To determine the mechanical causes of GB retraction, we conducted three series of laser ablations. First, we made linear incisions in the GB. We find an anisotropy in the maximum wound expansion consistent with a tensile force generated by the AS and applied to segments located around the curve of the GB. Second, we separated a patch of cells from the rest of the GB. These isolated cells do not continue to elongate, but instead round up. Even so, they often continue moving in the same direction. Third, we ablated part of one side of the saddle-shaped AS. Cuts destroying the AS cells closest to the curve of the GB halt GB retraction. Other AS cuts slow it. Our results indicate that the AS plays a mechanical role in GB retraction by applying tensile force to the curve of the GB. [Preview Abstract] |
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