Bulletin of the American Physical Society
APS March Meeting 2015
Volume 60, Number 1
Monday–Friday, March 2–6, 2015; San Antonio, Texas
Session L48: Focus Session: Physics of Cellular Organization II |
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Sponsoring Units: DBIO Chair: S.M. Ali Tabei, University of Northern Iowa Room: 217C |
Wednesday, March 4, 2015 8:00AM - 8:12AM |
L48.00001: Genetic networks specifying the functional architecture of orientation domains in V1 Joscha Liedtke, Fred Wolf Although genetic information is critically important for brain development and structure, it is widely believed that neocortical functional architecture is largely shaped by activity dependent mechanisms. Here we show theoretically that mathematical models of genetic networks of principal neurons interacting by long range axonal morphogen transport can generate morphogen patterns that exactly prescribe the functional architecture of the primary visual cortex (V1) as experimentally observed. We analyze in detail an example genetic network that encodes the functional architecture of V1 by a dynamically generated morphogen pattern. We use analytical methods from weakly non-linear analysis [Cross \& Hohenberg 1993] complemented by numerical simulations to obtain solutions of the model. In particular we find that the pinwheel statistics are in quantitative agreement with high precision experimental measurements [Kaschube et al. 2010]. This theory opens a novel perspective on the experimentally observed robustness of V1's architecture against radically abnormal developmental conditions such a dark rearing [White et al. 2001]. Furthermore, it provides for the first time a scheme how the pattern of a complex cortical architecture can be specified using only a small genetic bandwidth. [Preview Abstract] |
Wednesday, March 4, 2015 8:12AM - 8:24AM |
L48.00002: Numerical simulations on active rod like particles as a model for the collective behavior of Myxococcus xanthus Manon Wigbers, Shashi Thutupalli, Joshua Shaevitz We study collective behavior of Myxococcus xanthus using numerical simulations. Under starvation conditions, these social bacteria organize into multi-cellular structures, called ``fruiting bodies,'' within which cells sporulate. During the process of fruiting body formation, cells show various collective motion patterns. One of the most striking of these patterns is the so called rippling motility, characterized by standing density waves of reversing bacteria. Similar rippling behaviour is also observed during predatory feeding of the bacteria. Until now, the principles underlying this rippling behavior are not fully elucidated. Analogous to the well studied liquid crystalline phases in condensed matter physics, the ordering of the baceria within these rippling waves resembles a smectic like layered structure. In contrast to active nematic liquid crystalline phases widely studied in recent times, this represents the first known empirical example of an active smectic phase. Inspired by single-cell resolution experimental data of the bacteria, we develop a modelof active rod like particles and use numerical simulations to study the organizing principles that drive the transitions between the various active liquid crystalline phases in the myxobacterial collective behavior. [Preview Abstract] |
Wednesday, March 4, 2015 8:24AM - 8:36AM |
L48.00003: Non-ergodic diffusion on quenched, scale-free disorder in two dimensions Gerald J. Lapeyre, Jr., Pietro Massignan, Carlo Manzo, Juan A. Torreno-Pina, Maria F. Garc\'{I}a-Parajo, Maciej Lewenstein We discuss our recently introduced models of diffsion on media with random diffusivity~[1] and their application to transport in cell membranes~[2]. We find that the diffusion shows weak ergodicity breaking, and compute the anomalous exponents as a function of model parameters. We also report recent results on criteria for prediciting weak ergodicity breaking in random walks on specific models of quenched, scale-free, random media. \\[4pt] [1] P. Massignan, C. Manzo, J. A. Torreno-Pina, M. F. Garc\'{i}a-Parajo, M. Lewenstein, G. J. Lapeyre, Jr., Phys. Rev. Lett. \textit{112} (2014) \\[0 pt] [2] C. Manzo, J.A. Torreno-Pina, P. Massignan, G.J. Lapeyre Jr., M. Lewenstein, M. F. Garcia-Par\'ajo, arXiv:1407.2552 [Preview Abstract] |
Wednesday, March 4, 2015 8:36AM - 8:48AM |
L48.00004: Growth Kinetics of Intracellular RNA/Protein Droplets: Signature of a Liquid-Liquid Phase Transition? Joel Berry, Stephanie C. Weber, Nilesh Vaidya, Lian Zhu, Mikko Haataja, Clifford P. Brangwynne Nonmembrane-bound organelles are functional, dynamic assemblies of RNA and/or protein that can self-assemble and disassemble within the cytoplasm or nucleoplasm. The possibility that underlying intracellular phase transitions may drive and mediate the morphological evolution of some membrane-less organelles has been supported by several recent studies. In this talk, results from a collaborative experimental-theoretical study of the growth and dissolution kinetics of nucleoli and extranucleolar droplets (ENDs) in \textit{C. elegans} embryos will be presented. We have employed Flory-Huggins solution theory, reaction-diffusion kinetics, and quantitative statistical dynamic scaling analysis to characterize the specific growth mechanisms at work. Our findings indicate that both in vivo and in vitro droplet scaling and growth kinetics are consistent with those resulting from an equilibrium liquid-liquid phase transition mediated by passive nonequilibrium growth mechanisms - simultaneous Brownian coalescence and Ostwald ripening. This supports a view in which cells can employ phase transitions to drive structural organization, while utilizing active processes, such as local transcriptional activity, to fine tune the kinetics of these phase transitions in response to given conditions. [Preview Abstract] |
Wednesday, March 4, 2015 8:48AM - 9:00AM |
L48.00005: External stimulation strength controls actin response dynamics in Dictyostelium cells Hsin-Fang Hsu, Christian Westendorf, Marco Tarantola, Vladimir Zykov, Eberhard Bodenschatz, Carsten Beta Self-sustained oscillation and the resonance frequency of the cytoskeletal actin polymerization/depolymerization have recently been observed in Dictyostelium, a model system for studying chemotaxis. Here we report that the resonance frequency is not constant but rather varies with the strength of external stimuli. To understand the underlying mechanism, we analyzed the polymerization and depolymerization time at different levels of external stimulation. We found that polymerization time is independent of external stimuli but the depolymerization time is prolonged as the stimulation increases. These observations can be successfully reproduced in the frame work of our time delayed differential equation model. [Preview Abstract] |
Wednesday, March 4, 2015 9:00AM - 9:12AM |
L48.00006: Fluorescent BODIPY Rotor: Viscometer for Cellular Organelles and Membrane-Mimicking Vesicles J. Kimball, S. Raut, R. Fudala, H. Doan, B. Maliwal, N. Sabnis, A. Lacko, I. Gryczynski, S. Dzyuba, Z. Gryczynski Many cellular processes, such as mass and signal transport, metabolism and protein-protein interactions are governed in part by diffusion, and thus affected by their local microviscosity. Changes in this microviscosity has also been linked to various diseases, including atherosclerosis, Alzheimer's disease and diabetes. Therefore, directly measuring the heterogeneous viscosity of cellular constitutes can lead to greater understanding of these processes. To this effect, a novel homodiemeric BODIPY dye was evaluated as a fluorescent rotor probe for this application. A linear dependence on viscosity in the range of typical cellular microviscosity was established for steady-state and time-resolved properties of the dye. It was then embedded \textit{in vitro} to membrane-mimicking lipid vesicles (DPPC, POPC, and POPC plus cholesterol) and results indicated it to be a viable sensor for lifetime-based determination of microviscosity. The BODIPY dye was lastly endocytosed by SKOV3 cells and Fluorescence Lifetime Imaging Microscopy (FLIM) was performed, successfully mapping the viscosity of internal cell components. [Preview Abstract] |
Wednesday, March 4, 2015 9:12AM - 9:24AM |
L48.00007: Nanotopography-induced symmetry-breaking and guidance of actin polymerization waves and cell migration Wolfgang Losert, Can Guven, Xiaoyu Sun, John Fourkas, Anders Carlsson, Meghan Driscoll Many types of eukaryotic cells on a surfaces exhibit reaction diffusion-type waves of actin polymerization. Exposing migrating Dictyostelium discoideum cells to asymmetries at a length scale relevant to actin waves (300 nm) results in guidance of actin polymerization and of the migration of the cells themselves. Quantitative measurements of actin wave speed and direction distributions show that actin polymerization is preferentially localized to nanoridges and directed along the ridges, and that the velocity of guided actin polymerization waves decreases with decreasing ridge spacing. A stochastic growth model of actin polymerization dynamics reproduces these key observations. [Preview Abstract] |
Wednesday, March 4, 2015 9:24AM - 9:36AM |
L48.00008: Quantifying and controlling collective motion in externally guided cells Joshua Parker, Can Guven, Chenlu Wang, Edward Ott, Wolfgang Losert ~Many motile cells use chemical signals to coordinate their motion to aid in performing a larger task, be it healing a wound or aggregating to form a spore. This coordination can vary from subtle variations in overall alignment to broad, visibly structured patterns. Of particular interest of study are two organisms We introduce a model for motion towards a chemical signal and study these spatio-temporal correlations in the context of autocrine relay, such as seen in~Dictyostelium~discoideum, where we demonstrate that adhesion and chemical degradation both enhance visible ``streaming'' structures. We also study a model of paracrine signal relay relevant to human neutrophil migration and demonstrate how temporally varying chemical signals can be used to coordinate cell migration. We discuss both of these results in the context of their relevance to the survival of the organism and highlight future experimental tests. [Preview Abstract] |
Wednesday, March 4, 2015 9:36AM - 9:48AM |
L48.00009: The effects of out-of-plane curvature on the growth of epithelia Hannah Yevick, Guillaume Duclos, Isabelle Bonnet, Pascal Silberzan Collective cell migration is at play in many well documented in vivo processes for example, wound re-epithelialization, cancer metastasis and dorsal closure. We present a study describing the effect of out of plane curvature on the collective properties of epithelial tissue. Microfabricated environments are used to deconstruct a monolayer's response to geometry. Specifically, fibers with a radius of curvature between 1um-100um are populated with MDCK cells, a model epithelial, kidney-derived, cell line. Migration dynamics as well as cell architecture are quantified and the effects of curvature compared with confinement alone. Large curvatures trigger specific cellular behaviors and organization that may shed light on tubulogenesis. [Preview Abstract] |
Wednesday, March 4, 2015 9:48AM - 10:24AM |
L48.00010: Glycosylases utilize ``stop and go'' motion to locate DNA damage Invited Speaker: Shane Nelson Oxidative damage to DNA results in alterations that are mutagenic or even cytotoxic. Base excision repair is a mechanism that functions to identify and correct these lesions, and is present in organisms ranging from bacteria to humans. DNA glycosylases are the first enzymes in this pathway and function to locate and remove oxidatively damaged bases, and do so utilizing only thermal energy. However, the question remains of how these enzymes locate and recognize a damaged base among millions of undamaged bases. Utilizing fluorescence video microscopy with high spatial and temporal resolution, we have observed a number of different fluorescently labeled glycosylases (including bacterial FPG, NEI, and NTH as well as mammalian MutyH and OGG). These enzymes diffuse along DNA tightropes at approximately 0.01$+$/- 0.005 $\mu$m2/s with binding lifetimes ranging from one second to several minutes. Chemically induced damage to the DNA substrate causes a $\sim$ 50{\%} reduction in diffusion coefficients and a $\sim$ 400{\%} increase in binding lifetimes, while mutation of the key ``wedge residue'' -- which has been shown to be responsible for damage detection - results in a 200{\%} increase in the diffusion coefficient. Utilizing a sliding window approach to measure diffusion coefficients within individual trajectories, we observe that distributions of diffusion coefficients are bimodal, consistent with periods of diffusive motion interspersed with immobile periods. Utilizing a unique chemo-mechanical simulation approach, we demonstrate that the motion of these glycosylases can be explained as free diffusion along the helical pitch of the DNA, punctuated with two different types of pauses: 1) rapid, short-lived pauses as the enzyme rapidly probes DNA bases to interrogate for damage and, 2) less frequent, longer lived pauses that reflect the enzyme bound to and catalytically removing a damaged base. These simulations also indicate that the wedge residue is critical for interrogation and recognition of damage, and thus enzymes missing this residue diffuse faster. Similarly, chemically induced damage increases the frequency with which the enzymes encounter damaged bases, resulting in slower diffusion. [Preview Abstract] |
Wednesday, March 4, 2015 10:24AM - 10:36AM |
L48.00011: Silicon Micropore based Electromechanical Transducer to Differentiate Tumor Cells Waqas Ali, Muhammad U. Raza, Raja R. Khanzada, Young-Tae Kim, Samir M. Iqbal Solid-state micropores have been used before to differentiate cancer cells from normal cells using size-based filtering. Tumor cells differ from normal ones not only in size but also in physical properties like elasticity, shape, motility etc. Tumor cells show different physical attributes depending on the stage and type of cancer. We report a micropore based electromechanical transducer that differentiated cancer cells based on their mechanophysical properties. The device was interfaced with a high-speed patch-clamp measurement system that biased the ionic solution across the silicon-based membrane. The bias resulted in the flow of ionic current. Electrical pulses were generated when cells passed through. Different cells depicted characteristic pulses. Translocation profiles of cells that were either small or were more elastic and flexible caused electrical pulses shorter in widths and amplitudes whereas cells with larger size or lesser elasticity/flexibility showed deeper and wider pulses. Three non-small cell lung cancer (NSCLC) cell lines NCI-H1155, A549 and NCI-H460 were successfully differentiated. NCI-H1155, due to their comparatively smaller size, were found quickest in translocating through. The solid-sate micropore based electromechanical transducer could process the whole blood sample of cancer patient without any pre-processing requirements and is ideal for point-of-care applications. [Preview Abstract] |
Wednesday, March 4, 2015 10:36AM - 10:48AM |
L48.00012: Terasaki Ramps in the Endoplasmic Reticulum: Structure, Function and Formation Greg Huber, Jemal Guven, Dulce-Maria Valencia The endoplasmic reticulum (ER) has long been considered an exceedingly important and complex cellular organelle in eukaryotes (like you). It is a membrane structure, part folded lamellae, part tubular network, that both envelopes the nucleus and threads its way outward, all the way to the cell's periphery. Despite the elegant mechanics of bilayer membranes offered by the work of Helfrich and Canham, as far as the ER is concerned, theory has mostly sat on the sidelines. However, refined imaging of the ER has recently revealed beautiful and subtle geometrical forms -- simple geometries, from the mathematical point of view -- which some have called a ``parking garage for ribosomes.'' I'll review the discovery and physics of Terasaki ramps and discuss their relation to cell-biological questions, such as ER and nuclear-membrane re-organization during mitosis. Rather than being a footnote in a textbook on differential geometry, these structures suggest answers to a number of the ER's structure-function problems. [Preview Abstract] |
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