Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session F64: Physics of the Cytoskeleton Across Scales IIFocus
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Sponsoring Units: DBIO GSOFT Chair: Loren Hough Room: BCEC 259B |
Tuesday, March 5, 2019 11:15AM - 11:51AM |
F64.00001: Physical Guidance of Cytoskeletal Dynamics Invited Speaker: Wolfgang Losert The guided migration of cells is a complex dynamical process involving carefully regulated polymerization and depolymerization of the elements of the cellular scaffolding, in particular actin. Recent work has shown that polymerizing and depolymerizing actin can be described as an excitable system which exhibits natural waves or oscillations on scales of hundreds of nm, and that wave-like dynamics can be seen in a wide range of natural contexts. I will show that surface nanotopography on scales observed in vivo nucleates and guides the wave-like dynamics of actin polymerization, and that such guided actin waves control cell migration for a broad range of cell types. Furthermore controlled actin waves provide a simple framework to understand seemingly complex aspects of cell migration including the response to chemical and electrical guidance cues, and the ability of cells to follow each other precisely in streams. Thus the excitable systems character of the cellular scaffolding provides a simple, universal framework for analyzing guided migration in living systems. |
Tuesday, March 5, 2019 11:51AM - 12:03PM |
F64.00002: Fluctuation-driven contractility without motors Sihan Chen, Tomer Markovich, Frederick MacKintosh Contractility in cells is usually due to molecular motor activity, such as in the case of the contractile ring, in which actin and myosin generate during cytokinesis. Recent experiments, however, have suggested non-motor-based contraction in some cells. Here, we present a model for contraction based on stochastic binding of actin filaments that are known to have an asymmetric force response. This leads to continuous net contraction via a Brownian ratchet-like mechanism, provided that the crosslinking is active and violates detailed balance. Using this model, we calculate the force-velocity relation and find a stall force for the system, which could be used to test this model. |
Tuesday, March 5, 2019 12:03PM - 12:15PM |
F64.00003: Regulation of Pulsed Contraction of Actomyosin Networks Jing Li, Qilin Yu, Michael Murrell, Taeyoon Kim Actomyosin contractility regulates various biological processes including cell migration and cytokinesis. Cell cortex underlying a membrane, which is a representative actomyosin network in eukaryote cells, exhibits dynamic contractile behaviors. Interestingly, the cell cortex shows reversible aggregation of actin and myosin called pulsatile contraction in diverse cellular phenomena. While contractile behaviors of actomyosin machinery have been studied extensively in several in vitro and computational studies, none of them successfully reproduced pulsed contraction observed in vivo. In this study, we first reproduced the pulsed contraction only with the mechanical and dynamic behaviors of cytoskeletal components. We found that clusters with physiologically relevant size and duration can appear in the presence of both F-actin turnover and angle-dependent F-actin severing resulting from buckling induced by motor activities. In addition, we showed that RhoA signaling regulating the dynamics of F-actin and myosin can enhance the stability and durability of pulsed clusters. Our study sheds light on the underestimated significance of F-actin dynamics for the pulsed contraction and on the cooperative mechanism between mechanical and biochemical factors. |
Tuesday, March 5, 2019 12:15PM - 12:27PM |
F64.00004: Regulation of Motions of Myosin Motors in the Actin Cortex Wonyeong Jung, Ali Tabei, Taeyoon Kim Active transport driven by molecular motors in the cytoskeleton plays an important role in various cellular processes. It has been hypothesized that motions of myosin motors in the cortex are determined by the architecture of the cortex. However, the effects of dynamic, force-dependent behaviors of cytoskeletal components on myosin motors remain elusive despite their potential importance. In this study, we employed an agent-based computational model to study motions of myosin in the cell cortex. The model accounts for possible governing factors, including force-dependent walking of motors and the turnover of cross-linkers and F-actin. We found that motions of motors can be suppressed due to three reasons. Motors can slow down significantly either by local force generation or global force transmission between motors. It is also possible F-actin aggregation prevents motors from consistently walking. However, F-actin turnover can recover motor motility in all three cases by inducing force relaxation on motors and cross-linkers. Our results shed light on how myosin motions are regulated by many factors in vivo. |
Tuesday, March 5, 2019 12:27PM - 12:39PM |
F64.00005: Dynamics of focal adhesion orientation in response to time varying stretch Rumi De Mechanical forces play a central role in determining cell function and fate. The effect of time varying stretch is particularly striking which affects many cellular processes such as adhesion, orientation, migration, wound healing to name a few. Focal adhesions act as mechanosensors and in turn regulate the response of cells in tissues. It is not yet well understood how the stretch induces cytoskeletal organization, or how it affects the assembly of focal adhesions. We present a simple theoretical model based on a novel approach in the understanding of stretch sensitive bond association and dissociation processes together with the elasticity of the cell-substrate system to predict the growth, stability and the orientation of focal adhesions in the presence of static as well as cyclic stretches. Our model agrees well with several experimental observations; most importantly, it explains the puzzling observations of parallel orientation of focal adhesions under static stretch and nearly perpendicular orientation in response to fast varying cyclic stretch. Moreover, it also elucidates the existence of threshold frequency and stretch magnitude for orientational response that have been found to vary across cell types. |
Tuesday, March 5, 2019 12:39PM - 12:51PM |
F64.00006: Mechanism of Generating Pulling Force via Actin Polymerization Fowad Motahari, Anders Carlsson Actin polymerization is the primary mechanism for overcoming the large turgor pressure that opposes endocytosis in yeast. Actin-based pulling forces are less well understood than pushing forces. We stochastically simulate a system of 144 semiflexible actin filaments in a square network, treating all subunits explicitly. Each filament interacts with the membrane via a potential having both attractive and repulsive components. The protein Sla2, which binds actin filaments to the membrane, is assumed to slow the growth of the filaments near the array center by having a strongly attractive potential. The (de)polymerization rates depend on the filament-membrane gap. We include both actin network elasticity and filament-tip bending. We find that that the outer filaments push on the membrane, while the inner filaments pull on it. We calculate the force distribution for various model parameters, including the potential depths, the free filament on- and off-rates, the numbers of fast- and slow-growing filaments, and the network rigidity. Under the most favorable conditions, the total pulling force is the sum of the stall forces of all the pushing filaments. |
Tuesday, March 5, 2019 12:51PM - 1:03PM |
F64.00007: The role of the actin filament brancher Arp2/3 in the dynamics and structures of actomyosin networks James Liman, Carlos A. Bueno, Yossi Eliaz, Peter Wolynes, Herbert Levine, Margaret Cheung Actomyosin network contractility underlies the motility and division of a cell, involving contraction and expansion that are driven by active protein motors and actin treadmilling. In this work, we present novel computational and theoretical approaches to model contractility and growth in actomyosin networks and evaluate the spatiotemporal patterns of actin reorganization. We consider two different actomyosin network morphologies, unbranched and branched. For the unbranched case, the system includes motor proteins (non-muscle myosin IIA (NMIIA)) and cross-linker proteins (α-actinin). For the branched case, the system includes a third component—Arp2/3 complexes—that allows us to investigate the role of branching in actomyosin contractility. We observe that linkers modulate contraction in the unbranched and the branched actomyosin networks. The branched actomyosin networks relax more slowly than their unbranched counterparts. However, the branched networks show pronounced convulsive contractions. We expect our results to give an insight into the importance of the branched morphological formation in enhancing contractility of the actomyosin networks. |
Tuesday, March 5, 2019 1:03PM - 1:15PM |
F64.00008: Actin Dynamics Measured and Characterized by Optical Flow Leonard Campanello, Rachel Lee, Matt J. Hourwitz, John T Fourkas, Wolfgang Losert Actin dynamics are an important component of critical functions such as cell migration and immune response. Specifically, waves of actin are present in a wide range of conditions such as cell-cell adhesion formation and immune cell activation. We utilize periodic surface topographies comparable in size to in vivo collagen fiber networks to generate actin dynamics consistent with what would be observed in real cell microenvironments. We show that, when in contact with such textured surfaces, many cell types exhibit esotaxis – guidance of the actin waves by the surface texture. The one-dimensional waves of actin are very reproducible, which allows us to quantify these actin dynamics in cell types with dissimilar migratory modes and physiological purposes – slowly migrating epithelial MCF10A cells and fast migrating neutrophil-like HL60 cells. Using a computer vision algorithm called Optical Flow, we designed and employed an automated analysis program to characterize the pixel scale guidance of actin waves, as well as their mesoscale characteristics. |
Tuesday, March 5, 2019 1:15PM - 1:27PM |
F64.00009: Epithelial Wound Healing Coordinates Distinct Actin Network Architectures to Conserve Mechanical Work and Balance Power Alan Tabatabai, Visar Ajeti, Andrew Fleszar, Michael F Staddon, Daniel S. Seara, Christian Suarez, Muhammad Yousafzai, Dapeng Bi, Dave Kovar, Shiladitya Banerjee, Michael Murrell How cells with diverse morphologies and cytoskeletal architectures modulate their mechanical behaviors to drive robust collective motion within tissues is poorly understood. During wound repair within epithelial monolayers in vitro, cells coordinate the assembly of branched and bundled actin networks to regulate the total mechanical work produced by collective cell motion. Using traction force microscopy, we show that the balance of actin network architectures optimizes the wound closure rate and the magnitude of the mechanical work. These values are constrained by the effective power exerted by the monolayer, which is conserved and independent of actin architectures. Using a cell-based physical model, we show that the rate at which mechanical work is done by the monolayer is limited by the transformation between actin network architectures and differential regulation of cell-substrate friction. These results and our proposed mechanisms provide a robust quantitative model for how cells collectively coordinate their non-equilibrium behaviors to dynamically regulate tissue-scale mechanical output. |
Tuesday, March 5, 2019 1:27PM - 1:39PM |
F64.00010: Molecular crowding modulates actin filament mechanics and structure Nicholas Castaneda, Myeongsang Lee, Hector Rivera-Jacquez, Ryan Marracino, Theresa Merlino, Hyeran Kang The cellular environment is crowded with macromolecules that reduce accessible volume for biomolecule interactions and protein assembly. Actin filament assembly and mechanics play critical roles in many cellular functions including structural support, cell movement, and force generation. Although the effects of molecular crowding on actin assembly have been shown, how crowded environments affect filament conformations and mechanical properties remain unclear. Here, we investigate the effects of molecular crowding on actin filament mechanics and structure both in vitro and in silico. Direct visualization of filaments in the presence of crowders allows for the quantification of filament thermal bending dynamics and mechanics. Biophysical analysis show that molecular crowding enhances filament's effective bending stiffness and reduces average filament lengths. Utilizing molecular dynamics simulations, we demonstrate that molecular crowding leads to changes in filament conformations and inter-subunit contacts affecting filament mechanics. This work suggests that the interplay between excluded volume effects and non-specific interactions induced by molecular crowding may modulate actin filament mechanics and structure. |
Tuesday, March 5, 2019 1:39PM - 1:51PM |
F64.00011: How multivalent crosslinker proteins affect the self-assembly of actomyosin networks Yossi Eliaz, Margaret Cheung Actomyosin networks are nonequilibrium active matter systems with millions of nanometer-scale proteins that self-assemble to form complex biomechanical structures 10,000 times larger than its constituent proteins. These networks play a key role in the morphology of neuronal dendritic spines whose plasticity regulates long-term memory formation and retention. We use a coarse-grained model to simulate actomyosin networks with both active and passive multivalent crosslinker proteins. Passive crosslinkers bind filaments statically while active crosslinkers (motor proteins) exert force and walk along the polarized filaments. So far, only systems with divalent crosslinkers have been simulated in large scales. Our computational simulations allow us to understand how and when active and passive multivalent crosslinkers promote bundled, scaffolded, isotropic, or clustered phases of the networks. More specifically, our model reveals the dependencies between the network structure and the multivalent crosslinker’s type, concentration, and properties. |
Tuesday, March 5, 2019 1:51PM - 2:03PM |
F64.00012: Tug-of-war by active gel shapes positioning symmetry in cell-sized compartment Ryota Sakamoto, Masatoshi Tanabe, Tetsuya Hiraiwa, Kazuya Suzuki, Shin'ichi Ishiwata, Yusuke T. Maeda, Makito Miyazaki Force generation powered by actin cytoskeleton is underlying a wide range of phenomena from heart beating to cell migration [1]. To understand the underlying physical principles, in vitro reconstruction of actin cytoskeleton in water-in-oil droplet has been developed as a cell model, in which spontaneous F-actin flow and actomyosin clusters were self-organized [2]. However, it remains unclear how the spatial positioning of these structure is determined. To understand actomyosin-mediated geometric positioning, we confined actomyosin droplets in quasi two-dimensional chamber. We find that periodic actomyosin waves move the cluster to center, while the cluster is towed to edge by percolation of radial actomyosin network. By considering time-lag between maturation of actomyosin cortex and that of percolated network, active gel model recovers size-dependent two-state cluster positioning, which will give insights into the nucleus and spindle positioning in vivo [3]. We revealed active role of physical confinement to control intracellular positioning through actin cytoskeleton. |
Tuesday, March 5, 2019 2:03PM - 2:15PM |
F64.00013: Dynamic stiffening and softening of a system of colloids cross-linked via polymers Elisabeth Rennert, Gaston Moorhead, Jennifer Ross, Michael Rust, Rae Robertson-Anderson, Moumita Das With the goal of deciphering the design principles for biomimetic materials that can autonomously stiffen and soften, we investigate colloids as a model system that can dynamically transition between fluid-like and gel-like states when crosslinked with polymers. The model is first developed with a system of colloids interacting via Lennard Jones potential, a fraction of which are further connected via passive crosslinkers. We study this system using Brownian Dynamics simulations and obtain collective properties, such as the time needed to form system spanning networks and elastic moduli, for various colloid volume fractions, interaction strengths, and cross-linker concentrations. Using experimental parameters for polystyrene spheres and Bovine Serum Albumin (BSA) crosslinkers, we predict the behavior of real systems. Next, we replace the passive, one-shot crosslinkers in our model by active cross-linkers that can dynamically attach and detach, and characterize the degree of order and the mechanical response of the system as a function of time. Our results provide insights into the design of self-sustaining soft materials that can dynamically stiffen and soften, and how the properties of such materials can be tuned. |
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