Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session C66: Morphogenesis III |
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Sponsoring Units: DBIO GSNP GSOFT Chair: PAOLA NARDINOCCHI, Sapienza University of Rome Room: BCEC 261 |
Monday, March 4, 2019 2:30PM - 2:42PM |
C66.00001: Mechanical feedback maintains polarization in budding yeast mating projection growth Samhita Banavar, Michael Trogdon, Brian Drawert, Linda R Petzold, Otger Campas Cell Polarization is one of the commonly studied cases of spontaneous symmetry breaking in cells and controls many cellular processes, including morphogenesis, in budding yeast. However, the mechanisms that coordinate continued polarization to the growth region during mating projection formation, and the subsequent change in geometry from a spherical cell, remain unknown. We theoretically show that a genetically-encoded mechanical feedback relaying information about cell’s geometry is sufficient to maintain key polarity molecules and growth machinery remain localized to the site of growth. We have demonstrated that this same feedback mechanism also results in cell wall stability. |
Monday, March 4, 2019 2:42PM - 2:54PM |
C66.00002: Active mechanics in the growth of a bacterial cell wall Jordan Price, Giacomo Po, Alexander Jacob Levine, Jeff Eldredge It is well known that rod-shaped bacterial cell walls---a thin shell made of a disordered peptidoglycan network---grow rapidly in length. This speed allows cells to divide several times per hour. However, fast growth requires the cell to rapidly add material to a highly pressurized (osmotically) shell without bursting. The basic mechanism for growth is actively driven dislocations plowing through the shell in the circumferential direction. These motor-driven defects introduce new material (MreB filaments) into the shell but generate stress concentrations surrounding the moving defects. Motivated by the large deformations inherent in bacterial growth, we develop a nonlinear continuum mechanics model with actively driven dislocations to describe the growth of the cell wall. Using numerical simulations, we study the interaction of stress fields that arise as these filaments are added to the existing peptidoglycan mesh. Furthermore, we investigate how the growth mechanics are affected by fluctuations in turgor pressure, and the presence of heterogeneities and defects in the cell wall that can form during an osmotic shock or antibiotic treatment. |
Monday, March 4, 2019 2:54PM - 3:06PM |
C66.00003: Limitations on Tissue Shape Control by Mechanical Feedback Alexander Golden, David K Lubensky How size and shape of living tissues are controlled is a fundamental question of developmental biology. What are the mechanisms that can produce correct sizes? How does size control relate to shape control? We investigate how size and shape control interact in a model of growth control in the Drosophila wing disc epithelium, which appears to achieve a robust final size. In particular, we study the capacity of mechanical feedback models to control not only tissue size, but tissue shape. We develop an analytic model capable of integrating mechanical feedback on tissue growth into an elastic theory. This allows us to make precise claims about the limitations of shape control by mechanical feedback, and demonstrate how these limitations derive from underlying elastic principles. |
Monday, March 4, 2019 3:06PM - 3:18PM |
C66.00004: Inflationary Embryology and the Statistical Physics of Noisy Tissue Growth Ojan Khatib Damavandi, David K Lubensky Tissue growth is fundamental to biology and is noisy. Noise has important implications for morphogenesis and tissue integrity, yet a basic theoretical description of noisy tissue growth has been lacking. Growth nonuniformity leads to a build-up of mechanical stresses, and many tissues respond to stress by modulating their growth. Then, how does the interplay between noise and stress feedback affect tissue growth, and what can we predict about the statistical properties of experimentally accessible quantities? We model the tissue as a continuum, elastic sheet undergoing exponential growth with mechanical feedback and find that the density-density correlations show power-law scaling in space. In anisotropic growth, the standard deviation in clone sizes is comparable to the mean, in contrast to the isotropic case where relative variations in clone size vanish at long times. The high variability in clone statistics observed in anisotropic growth is due to the presence of two soft growth modes, which generate no stress. Our work analyzes the simplest model of noisy growth of elastic tissues. It thus both introduces a new class of nonequilibrium growth models and represents a first step towards understanding specific biological contexts. |
Monday, March 4, 2019 3:18PM - 3:30PM |
C66.00005: Biophysically Inspired Morphometrics Salem Al Mosleh, Gary P. T. Choi, L Mahadevan Motivated by the quest to understand shape changes in biology, both in a developing organism and over evolutionary time scales, we develop a computational framework for analyzing geometric shape changes between surfaces embedded in three dimensions. Our approach allows us to simultaneously solve the problem of registration and the morphing of shapes onto each other using biophysically inspired distance functions. We then discuss how this framework can be used to analyze shape changes in such instances as planar wings and human faces. |
Monday, March 4, 2019 3:30PM - 3:42PM |
C66.00006: Dynamic Morphoskeleton Mattia Serra, Sebastian Streichan, L Mahadevan During embryonic development, cells undergo large-scale motion generating tissues rearrangement, which ultimately defines the final shape of the embryo. While developmental biology has identified several genes driving local cellular processes, the interplay between cell-intrinsic and external stresses is fairly less understood because several local mechanisms are still unknown or hard to measure. By contrast, with the significant advances in live imaging techniques, it is now possible to fully track cell trajectories. Using ideas from nonlinear dynamics, we propose a rigorous objective kinematic framework for analyzing cell motion, which uncovers the underlying dynamic morphoskeleton, i.e. the centerpieces of cell trajectory patterns in space and time. The dynamic morhposkeleton provides a quantitative tool for comparing different morphogenetic phenotypes, quantifying the impact of genetic and physical manipulations, studying cell fate, and overall bridging the gap between bottom-up and top-down modeling approaches. We illustrate our results on a Drosophila gastrulation dataset obtained by in toto light-sheet microscopy. |
Monday, March 4, 2019 3:42PM - 3:54PM |
C66.00007: Morphology analysis based on information theory Vasyl Alba, Madhav Mani, Richard Carthew, James Carthew We used machine vision and information theory approach to address a question of quantitative description of the morphological traits in biological systems. We used a population of fruit flies that was under developmental pressure to demonstrate the potential of the newly developed method. In particular, we changed diet and temperature to increase morphological variation. |
Monday, March 4, 2019 3:54PM - 4:06PM |
C66.00008: Activity driven buckling in early steps of organogenesis Francesco Serafin, Suraj Shankar, Benjamin Loewe, Boris I Shraiman, Mark Bowick, M. Cristina Marchetti Morphogenesis, the complex process by which the shape of organs and organisms emerges from cell organization, intertwines chemical and physical processes. In many situations, 3D biological structures are achieved through targeted active folding processes of 2D tissue layers. An example is the process of lumen formation – the buckling, folding and invagination of a planar cell sheet that leads to the formation of a hollow cavity enwrapped by a polarized epithelium. In this talk, starting with an active elastic continuum description of a cellular tissue layer of finite thickness, we derive an effective 2D model that includes contractility and cell division. We show that the model can account for the buckling instability at the onset of lumen formation. We find that traction localizes contractile stresses at the boundary of the tissue, while cell division induces an in-plane outward pressure. These two competing effects destabilize the initial planar state forcing the tissue to buckle. |
Monday, March 4, 2019 4:06PM - 4:18PM |
C66.00009: Active junctions as a pathway to stress generation in morphogenesis Silke Henkes, Ilyas Djafer-Cherif, Luke Coburn, Guillermo Serrano-Najera, Kees Weijer, Rastko Sknepnek During gastrulation, and other development stages like germ band extension, epithelial cell sheets spontaneously organise to exert contractile mechanical forces, resulting in convergence-extension flow. Current models assume different types of chemical signalling based pre-patterning of the junctions, leading to both tension and flow. Here we present a model of self-amplifying contractile cell sheets that posits a myosin-dependent junction contractility with a tension-dependent feedback loop. This active mechanics model leads to the spontaneous formation of tension chains with both isotropic characteristics and directionality in the presence of an applied stress. We discuss the necessary and sufficient ingredients for the local mechanics to generate chains, and then focus on the flow that results from the activated junctions. We find that disordered flow arises spontaneously, and characterize the conditions for convergence-extension flow using small active cell groups embedded in a passive matrix. |
Monday, March 4, 2019 4:18PM - 4:30PM |
C66.00010: Physical Aspects of Drosophila gastrulation. Konstantin Doubrovinski, Kranthi Mandadapu, Joel Tchoufag, Reza Farhadifar Despite a long-standing effort to uncover the physical principles governing animal morphogenesis, the knowledge of embryonic tissue mechanics remains elusive. We address the physical aspects of embryonic tissue mechanics using fruit fly gastrulation as a model. During this process, a subset of cells in the ventral part of the embryo constrict on one side and subsequently invaginate into the interior of the embryo, thereby causing the embryonic surface to form a furrow. To determine the mechanism of tissue shape change during gastrulation, we have developed a toolbox of biophysical methods that allow accurate quantification of material tissue properties in live fruit fly embryos. Specifically, we have developed magnetic tweezers exploiting either fluorescent magnetic microspheres or ferrofluid droplets, as well as flexible cantilevers microfabricated from PDMS, allowing highly quantitative measurements of the rheological properties in the early fly embryo. Our measurements directly translate into a predictive theory that explains key aspects of tissue dynamics during fruit fly gastrulation. Specifically, our model explains the marked anisotropy of tissue constriction in the initial phase of gastrulation as well as the mechanism of tissue invagination during the subsequent phase. |
Monday, March 4, 2019 4:30PM - 4:42PM |
C66.00011: External forces generated by the attachment between blastoderm and vitelline envelope impact gastrulation in insects Stefan Muenster, Alexander Mietke, Akanksha Jain, Pavel Tomancak, Stephan W Grill Gastrulation is a critical step during the development of multicellular organisms in which a single-layered tissue folds into a multi-layered germband. This shape change is characterized by tissue folding and large-scale tissue flow. The myosin-dependent forces that underlie this process have been increasingly investigated; however, thus far, the possible interaction between the moving tissue and the rigid shell surrounding the embryo has been neglected. Here, we present our quantitative findings on the physical mechanisms governing gastrulation in the red flour beetle, Tribolium castaneum. We investigated the forces expected within the tissue given the myosin distribution observed by multi-view light-sheet microscopy and discovered that an additional external force must be counteracting this tissue-intrinsic contractility. We then identified that a specific part of the tissue tightly adheres to the outer rigid shell. This attachment is mediated by a specific integrin whose knock-down leads to a complete loss of the counter-force. Moreover, in the fruit fly Drosophila melanogaster, knock-down of another integrin leads to a severe twist of the germband, suggesting that the integrin-mediated interaction between tissue and vitelline envelope may be conserved in insects. |
Monday, March 4, 2019 4:42PM - 4:54PM |
C66.00012: Optogenetic control of contractile tissue forces during Drosophila morphogenesis Marisol Herrera Perez, Karen E. Kasza Epithelial tissues undergo dramatic changes in shape during development. These changes are driven in large part by contractile forces generated by the actomyosin cytoskeleton of cells. In addition to physically shaping cells and tissues, mechanical forces can act as cues to influence cell behavior and could help coordinate cell behaviors across multicellular tissues. A major obstacle to dissecting the mechanisms of how mechanical forces shape tissues has been the lack of tools for precise manipulation of forces in vivo. To address this, we developed a collection of optogenetic tools to locally and systematically modulate actomyosin contractility in the Drosophila embryo. With these tools, we have demonstrated local, light-gated myosin recruitment, and changes in myosin localization patterns across tissues. Using these tools in combination with live confocal imaging and quantitative images analysis, we find that inducing contractile forces in small groups of cells in an epithelial tissue can deform and influence cell behaviors across the tissue in the developing embryo. These studies are shedding light on the roles of mechanical cues in coordinating cell behaviors in multicellular tissues during development. |
Monday, March 4, 2019 4:54PM - 5:06PM |
C66.00013: Coordination of epithelial cells during morphogenesis Matthias Häring, Prachi Richa, Jörg Großhans, Fred Wolf Epithelial cells are capable of sensing and reacting to the forces and movements of their neighbours. We fully quantify the dynamics of epithelial tissue using a novel high-throughput image analysis pipeline based on deep neural networks. Inspired by graph theory, we decompose cell-cell interactions into three distinct coupling types. With this approach, the epithelium can be represented by a planar graph of cell couplings whereby cells are interpreted as vertices and junctions between cells as edges. Utilizing graph-theoretic measures, we compare wild type tissue and mutants with impaired signal transduction capabilities revealing significant differences in e.g. composition of coupling types and spatial distributions. In contrast to the wild type, tension in those mutants is anisotropically distributed, indicating that local cell-cell coordination through mechano-sensing is essential for the function of an epithelium as force-generating tissue. |
Monday, March 4, 2019 5:06PM - 5:18PM |
C66.00014: Cell-cell adhesion in tissue mechanics and morphogenesis Xun Wang, Karen Kasza During development, simple epithelia reorganize into tissues with complex form and structure. Tissue reorganization during morphogenesis can be rapid. In Drosophila, cell rearrangements in the embryonic epithelium double the length of the body axis in 30 minutes. Adhesion at cell-cell contacts, mediated by junctional proteins, and contractile tension, generated by actomyosin, are thought to be key machineries controlling epithelial tissues. However, it remains unclear how the balance between adhesion and tension determines epithelial structure and mechanics. To gain insight, we are systematically modulating the balance between adhesion and tension in vivo. E-cadherin is a primary component of cell-cell adhesions. Using multiple approaches, we increase or decrease E-cadherin levels relative to wild type and use confocal imaging to study the effects on cell shapes and movements. We find that modulating adhesion influences cell shapes prior to the onset of axis elongation as well as cell rearrangement rates during elongation. We will discuss how our results compare to vertex model predictions. These systematic, quantitative experimental studies of tissue mechanics in vivo are an essential step in building models of morphogenesis. |
Monday, March 4, 2019 5:18PM - 5:30PM |
C66.00015: Superstretching epithelial sheets Ernest Latorre-Ibars, Sohan Kale, Xavier Trepat, Marino Arroyo During morphogenesis, cell monolayers need to change their shape in various ways. For instance, cell monolayers undergo very large stretching during blastocyst hatching in mammalian embryos. In this talk, I will discuss a mechanism by which epithelial tissues can withstand extreme stretches without significantly increasing tissue tension, which would otherwise compromise tissue integrity [1]. I will describe how, under applied tension, epithelial cells can adopt two "metastable" states, one in a barely stretched state, and one in a superstretched state. This phase coexistence allows tissues to further stretch at constant tension by switching cells into the super-stretched phase, in close analogy with the phenomenology of superelasticity exhibited by NiTi alloys or by intermediate filaments. In epithelial monolayers, this phenomenology has an active origin that depends on cytoskeletal dynamics. I will present experimental evidence of epithelial active superelasticity, a theoretical model explaining it and bridging from cytoskeletal dynamics to emergent material behavior, and will discuss the implications during morphogenesis. |
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