Bulletin of the American Physical Society
APS March Meeting 2016
Volume 61, Number 2
Monday–Friday, March 14–18, 2016; Baltimore, Maryland
Session B35: The Physics of Cellular OrganizationFocus
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Sponsoring Units: DBIO Chair: Michael Gramlich, Ali Tabei, Washington University, University of Northern Iowa Room: 338 |
Monday, March 14, 2016 11:15AM - 11:51AM |
B35.00001: Liquid-like bundles of crosslinked actin filaments contract without motors Invited Speaker: Kimberly Weirich The actin cytoskeleton is a dynamic, structural material that drives cellular-scale deformations during processes such as cell migration and division. Motor proteins are responsible for actively driving many deformations by buckling and translocating actin filaments. However, there is evidence that deformations, such as the constriction of the actin bundle that drives the separation of cells during division, can occur without motors, mediated instead by crosslinker proteins. How might crosslinkers, independent of motors, drive contraction of a bundle? Using a model system of purified proteins, we show that crosslinkers, analogous to molecular cohesion, create an effective surface tension that induces bundle contraction. Crosslinked short actin filaments form micron-sized spindle-shaped bundles. Similar to tactoid granules found at the isotropic-nematic phase transition in liquid crystals, these bundles coarsen and coalesce like liquid droplets. In contrast, crosslinked long filaments coarsen into a steady state of bundles that are frozen in a solid-like network. Near the liquid-solid boundary, filaments of intermediate length initially form bundles that spontaneously contract into tactoid droplets. Our results, that crosslinked actin bundles are liquid-like with an effective surface tension, provide evidence for a mechanism of motor-independent contractility in biological materials. [Preview Abstract] |
Monday, March 14, 2016 11:51AM - 12:03PM |
B35.00002: F-actin Severing Facilitates Distinct Mechanisms of Stress Relaxation in the Actin Cytoskeleton Taeyoon Kim, Wonyeong Jung, Michael Murrell Rheological behaviors of actin cytoskeleton play an important role in physiological processes including cell migration and division. The actin cytoskeleton shows a wide variety of viscoelastic responses to external mechanical cues, such as strain-stiffening and stress relaxation. It has been hypothesized that the stress relaxation originates mainly from transient nature of cross-linkers that connect pairs of F-actins. By contrast, potential impacts of rich F-actin dynamics to the stress relaxation have been neglected in most previous studies. Here, using a computational model, we demonstrated that severing of F-actins induced by buckling during strain-stiffening can facilitate a very distinct mode of stress relaxation in the actin cytoskeleton from that induced by the transient cross-linkers. We also explored conditions where the severing-induced stress relaxation becomes prominent. This finding provides a more complete understanding of rheological behaviors of the actin cytoskeleton. [Preview Abstract] |
Monday, March 14, 2016 12:03PM - 12:15PM |
B35.00003: A cycling state that can lead to glassy dynamics in intracellular transport Monika Scholz, Stanislav Burov, Kimberly L. Weirich, Bjorn J. Scholz, S.M Ali Tabei, Margaret L. Gardel, Aaron Dinner Power-law dwell times have been observed for molecular motors in living cells, but the origins of these trapped states are not known. We introduce a minimal model of motors moving on a two- dimensional network of filaments, and simulations of its dynamics exhibit statistics comparable to those observed experimentally. Analysis of the model trajectories, as well as experimental particle tracking data, reveals a state in which motors cycle unproductively at junctions of three or more filaments. We formulate a master equation for these junction dynamics and show that the time required to escape from this vortex-like state can account for the power-law dwell times. We identify trends in the dynamics with the motor valency for further experimental validation. We demonstrate that these trends exist in individual trajectories of myosin II on an actin network. We discuss how cells could regulate intracellular transport and, in turn, biological function, by controlling their cytoskeletal network structures locally. [Preview Abstract] |
Monday, March 14, 2016 12:15PM - 12:27PM |
B35.00004: Stochastic Molecular Transport on Microtubule Bundles with Structural Defects M.W. Gramlich, S.M. Ali Tabei Intracellular transport involves complex coordination of multiple components such as: the cytoskeletal network and molecular motors. Perturbations in this process can amplify over time and space, thereby affecting transport. One little studied component of transport are structural defects in the cytoskeletal network. In this talk we will present a stochastic model of the interaction of the molecular motor, kinesin-1, and a bundled cystoskeletal network of microtubules, and explicitly explore the role of microtubule ends (a type of defect) on long-range transport. We will show how different types of end distributions can ultimately result in the same observed transport behavior for bundles. We compare transport on completely uniform bundles, found in the axon, to completely random bundles, found in dendrites. Because of the un-biased random bundle nature, defects affect transport on dendrite bundles more than on uniform bundles in the axon. Further, defects act as large spatial-scale traps that result in random wait-times which have been assumed in previous models. [Preview Abstract] |
Monday, March 14, 2016 12:27PM - 12:39PM |
B35.00005: Size scaling of microtubule asters in confinement James Pelletier, Christine Field, Kaspars Krutkramelis, Nikta Fakhri, John Oakey, Jay Gatlin, Timothy Mitchison Microtubule asters are radial arrays of microtubules (MTs) nucleated around organizing centers (MTOCs). Across a wide range of cell types and sizes, aster positioning influences cellular organization. To investigate aster size and positioning, we reconstituted dynamic asters in \textit{Xenopus} cytoplasmic extract, confined in fluorous oil microfluidic emulsions. In large droplets, we observed centering of MTOCs. In small droplets, we observed a breakdown in natural positioning, with MTOCs at the droplet edge and buckled or bundled MTs along the interface. In different systems, asters are positioned by different forces, such as pushing due to MT polymerization, or pulling due to bulk or cortical dynein. To estimate different contributions to aster positioning, we biochemically perturbed dynactin function, or MT or actin polymerization. We used carbon nanotubes to measure molecular motions and forces in asters. These experimental results inform quantitative biophysical models of aster size and positioning in confinement. [Preview Abstract] |
Monday, March 14, 2016 12:39PM - 12:51PM |
B35.00006: The role of catch-bonds in acto-myosin mechanics and cell mechano-sensitivity Umut Akalp, Franck J. Vernerey Contraction and spreading of adherent cells are important phenomena in range of cellular processes such as differentiation, morphogenesis, and healing. In this presentation, we propose a novel mechanism of adherent cell mechano-sensing, based on the idea that the contractile acto-myosin machinery behaves as a catch-bond. For this, we construct a simplified model of the acto-myosin structure that constitute the building block of stress fibers and express the stability of cross-bridges in terms of the force-dependent bonding energy of the acto-myosin bond. Consistent with experimental measurements, we then consider that the energy barrier of the acto-myosin bond increases for tension and show that this response is enough to explain the force-induced stabilization of an SF. The resulting model eventually takes the form of a force-sensitive, active visco-elastic material, powered by ATP hydrolysis. The model is used to investigate the organization and contraction of the actin cytoskeleton of cells laying on arrays of microposts. Upon comparison with experimental observations and measurements, simulations show that the catch-bond hypothesis is satisfactory to predict the sensitivity of adherent cells to substrate stiffness as well as the complex organization of the actin cytoskeleton. [Preview Abstract] |
Monday, March 14, 2016 12:51PM - 1:27PM |
B35.00007: Feedback Interactions of Polymerized Actin with the Cell Membrane: Waves, Pulses, and Oscillations Invited Speaker: Anders Carlsson Polymerized filaments of the protein actin have crucial functions in cell migration, and in bending the cell membrane to drive endocytosis or the formation of protrusions. The nucleation and polymerization of actin filaments are controlled by upstream agents in the cell membrane, including nucleation-promoting factors (NPFs) that activate the Arp2/3 complex to form new branches on pre-existing filaments. But polymerized actin (F-actin) also feeds back on the assembly of NPFs. We explore the effects of the resulting feedback loop of F-actin and NPFs on two phenomena: actin pulses that drive endocytosis in yeast, and actin waves traveling along the membrane of several cell types. In our model of endocytosis in yeast, the actin network is grown explicitly in three dimensions, exerts a negative feedback interaction on localized patch of NPFs in the membrane, and bends the membrane by exerting a distribution of forces. This model explains observed actin and NPF pulse dynamics, and the effects of several interventions including i) NPF mutations, ii) inhibition of actin polymerization, and iii) deletion of a protein that allows F-actin to bend the cell membrane. The model predicts that mutation of the active region of an NPF will enhance the accumulation of that NPF, and we confirm this prediction by quantitative fluorescence microscopy. For actin waves, we treat a similar model, with NPFs distributed over a larger region of the cell membrane. This model naturally generates actin waves, and predicts a transition from wave behavior to spatially localized oscillations when NPFs are confined to a small region. We also predict a transition from waves to static polarization as the negative-feedback coupling between F-actin and the NPFs is reduced. [Preview Abstract] |
Monday, March 14, 2016 1:27PM - 1:39PM |
B35.00008: Whole Cell Model of Actin Diffusion and Reaction based on Single Molecule Speckle Microscopy Measurements Laura McMillen, Dimitrios Vavylonis It is debated whether transport of actin across the cell by diffusion alone is sufficiently fast to account for the rapid reorganization of actin filaments at the leading edge of motile cells. In order to investigate this question, we created a 3D model of the whole cell that includes reaction and diffusion of actin using a particle Monte Carlo method. For the lamellipodium of the simulated cell we use the model by Smith et al. Biophys. J 104:247 (2013), which includes two diffuse pools of actin, one which is slowly diffusing and the other which diffuses more quickly, as well as a pool of filamentous actin undergoing retrograde flow towards the cell center. We adjusted this model to fit a circular geometry around the whole cell. We also consider actin in the cell center which is either diffusing or in stationary filamentous form, representing cortical actin or actin in stress fibers. The local rates of polymerization and the lifetime distributions of polymerized actin were estimated from single molecule speckle microscopy experiments by the group of N. Watanabe. With this model we are able to simulate prior experiments that monitored the redistribution of actin after photoactivation or fluorescence recovery after photobleaching in various parts of the cell. We find that transport by diffusion is sufficient to fit these data, without the need for an active transport mechanism, however significant concentration gradients may develop at steady state. [Preview Abstract] |
Monday, March 14, 2016 1:39PM - 1:51PM |
B35.00009: Chemotaxis to Excitable Waves in Dictyostelium Discoideum Arpan Bhowmik, Wouter-Jan Rappel, Herbert Levine In recent years, there have been significant advances in our understanding of the mechanisms underlying chemically directed motility by eukaryotic cells such as Dictyostelium. In particular, the LEGI model has proven capable of providing a framework for quantitatively explaining many experiments that present Dictyostelium cells with tailored chemical stimuli and monitor their subsequent polarization. Here, we couple the LEGI approach to an excitable medium model of the cAMP wave-field that is self-generated by the cells and investigate the extent to which this class of models enables accurate chemotaxis to the cAMP waveforms expected in vivo. Our results indicate that the ultra-sensitive version of the model does an excellent job in providing natural wave rectification, thereby providing a compelling solution to the ``back-of-the-wave paradox'' during cellular aggregation. [Preview Abstract] |
Monday, March 14, 2016 1:51PM - 2:03PM |
B35.00010: Mechanical feedback stabilizes budding yeast morphogenesis Samhita Banavar, Michael Trogdon, Linda Petzold, Otger Campas Walled cells have the ability to remodel their shape while sustaining an internal turgor pressure that can reach values up to 10 atmospheres. This requires a tight and simultaneous regulation of cell wall assembly and mechanochemistry, but the underlying mechanisms by which this is achieved remain unclear. Using the growth of mating projections in budding yeast (S. \textit{cerevisiae}) as a motivating example, we have developed a theoretical description that couples the mechanics of cell wall expansion and assembly via a mechanical feedback. In the absence of a mechanical feedback, cell morphogenesis is inherently unstable. The presence of a mechanical feedback stabilizes changes in cell shape and growth, and provides a mechanism to prevent cell lysis in a wide range of conditions. We solve for the dynamics of the system and obtain the different dynamical regimes. In particular, we show that several parameters affect the stability of growth, including the strength of mechanical feedback in the system. Finally, we compare our results to existing experimental data. [Preview Abstract] |
Monday, March 14, 2016 2:03PM - 2:15PM |
B35.00011: Mechanical Trade-offs in Experimentally Evolved Multicellular Yeast Shane Jacobeen, Jennifer Pentz, William Ratcliff, Peter Yunker The evolution of multicellularity as much about physics as it is about biology, as selection acts on the physical properties of multicellular bodies. Nascent multicellular organisms are confronted by internal and external forces that act on large length scales and are capable of fracturing intercellular bonds. We study the evolution of the mechanical properties of multicellular `snowflake' yeast that were selected for increased size over \textasciitilde 1,500 generations$^{\mathrm{1,2}}$. While these snowflakes evolve to be larger by mitigating internal forces, they also become more susceptible to fracturing when faced with external compressive forces. Using confocal microscopy and direct mechanical measurements, we investigate the physical underpinnings and consequences of this strength-toughness trade-off. \textbf{References:} $^{\mathrm{1}}$W. Ratcliff \textit{et al.} 2012. PNAS. 109:1959--1600. $^{\mathrm{2}}$W. Ratcliff \textit{et al}. 2015. Nature Communications. 6:6102. [Preview Abstract] |
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