Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session P65: Active and Living Matter IIFocus
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Sponsoring Units: DBIO Chair: Azam Gholami, Max-Planck-Gesellschaft Room: BCEC 260 |
Wednesday, March 6, 2019 2:30PM - 3:06PM |
P65.00001: Tissue flow genetics: mapping the forces that shape complex organs Invited Speaker: Sebastian Streichan Developmental biology established principles of how the body plan is laid out, morphogens setup axes, and gene expression patterns determine cell fates - yet how the form of organs emerges from coordinated action of multiple domains of distinct cell types remains elusive. We combine in toto live imaging and automated data analysis with physical modeling to investigate the link between kinetics of global tissue transformations and patterns of force generation during Drosophila gastrulation. We find our visco-elastic model driven by stress proportional to the spatial distribution and anisotropy of two quantitatively measured myosin pools achieves a 90% accurate description of the measured tissue flow - using only 3 parameters. Our analysis shows (i) forces driving the flow arise from non-uniformity of stress, thus spatial myosin modulation is critical for dynamics. Long-range modulation of the anisotropic part along the Dorso-Ventral (DV) axis suggests a novel role for the DV patterning system in convergent extension. (ii) The relation between flow and myosin forcing is non-local, and a transition towards areal incompressibility during germband extension further enhances non-locality. (iii) Mutant analysis indicates mechanical feedback on myosin recruitment relating it to the local strain rate. We conclude that understanding morphogenetic flows requires a fundamentally global perspective. |
Wednesday, March 6, 2019 3:06PM - 3:18PM |
P65.00002: Quantifying the changes in cell morphology with changes in cell state Elaheh Alizadeh, Wenlong Xu, Jordan Castle, Jacqueline Foss, Ashok Prasad The shape of an adherent cell on a surface depends upon its active cytoskeletal properties and can change with a change in cell state. We have developed a large number of parameters to quantify cell shape and cytoskeletal morphology[1]. Using these to study different cell lines, as well as different experimental conditions, we show, with the help of statistical analysis and neural networks, that cell shape and cytoskeletal texture can discriminate between different states. Projections into lower-dimensional shape space allow us to distinguish between similar and dissimilar changes in shape, and identify similarities in shape changes between breast cancer and osteosarcoma cell lines accompanying the acquisition of invasive characteristics. We also discuss the similarities and differences between shape changes of different cell lines with similar experimental perturbations, as well as the heterogeneity in shape characteristics. Our data indicates that cellular morphology may be a powerful and sensitive window into the physiological state of the cell [2]. |
Wednesday, March 6, 2019 3:18PM - 3:30PM |
P65.00003: Loss of vimentin intermediate filaments increases motility and nuclear damage in confining spaces Alison Koser Patteson, Paul Janmey Cell migration is important to many biological processes, such as embryogenesis, wound healing, and cancer metastasis. The proper migration of cells is regulated by the mechanical properties of the cytoskeleton. The cytoskeleton is comprised of three main polymers, F-actin, microtubules, and intermediate filaments. When cells transition from stationary to migratory states, they often upregulate the intermediate filament vimentin. The viscoelasticity of vimentin networks in shear deformation has been documented, but its role in motility remains largely mysterious. Here, we used mouse embryo fibroblasts derived from wild-type and vimentin-null mice and examined their migration in microfluidic constrictions. We find that loss of vimentin increases 3D motility, unlike on rigid 2D substrates. Migrating through small constrictions leads to stress-induced nuclear damage in the form of blebs, nuclear envelope rupture, and double-stranded DNA breaks. These nuclear damage markers increase in the absence of a filamentous vimentin network. Our findings indicate that vimentin hinders 3D motility by providing mechanical resistance against large strains and thereby protects the structural integrity of the cell. |
Wednesday, March 6, 2019 3:30PM - 3:42PM |
P65.00004: Probing the mechanical organization of k-fiber microtubule bundles within the mammalian mitotic spindle via targeted laser ablation and speckle microscopy Marcus A Begley, Elizabeth Mae Davis, Mary Williard Elting In dividing cells, a self-assembling microtubule-based machine called the mitotic spindle segregates chromosomes, ensuring that each new daughter cell has exactly one copy of its genetic information. Spindle microtubule organization imparts shape and structural robustness. For example, bundles of microtubules called kinetochore-fibers (k-fibers) attach chromosomes to the spindle and exert force to align and ultimately segregate them. Thus, the mechanical integrity of the k-fiber is critical to spindle function, yet its organization is not well-understood. For example, we do not fully understand how molecules that crosslink microtubules along k-fiber lengths contribute to overall k-fiber mechanics, nor whether k-fiber microtubules remain rigidly associated or fluidly slide past each other in response to spindle dynamics. To address these questions, we are probing the mechanics of inter-microtubule associations within the k-fiber by single-molecule speckle microscopy and by severing k-fibers via laser ablation. Our initial results suggest that k-fiber microtubules associate along their lengths and primarily act in the spindle as single rigid objects, but that connections between their microtubules are weak enough to be disrupted by our mechanical perturbations. |
Wednesday, March 6, 2019 3:42PM - 3:54PM |
P65.00005: Stress-stabilized sub-isostatic fiber networks in a rope-like limit Sadjad Arzash, Jordan Shivers, Albert James Licup, Abhinav Sharma, Fred C. MacKintosh Biological networks are common in both intercellular and extracellular environments. Mechanics of these disordered fibrous networks is strongly dependent on their local coordination number. It is observed that real biopolymer networks have connectivity between three and four. Such networks are sub-isostatic with only central force interactions, but exhibit a mechanical phase transition between floppy and rigid states under shear. Introducing weak bending interactions stabilizes these networks and decreases the critical signatures of this transition. We show that applying external stresses on a sub-isostatic network with only tensile central force interactions, i.e., a rope-like potential also stabilizes these systems. Moreover, we find that the linear shear modulus shows a power law scaling with the external normal stress, with a non-mean-field exponent. We also find a critical strain that shifts to lower values under prestress. Applied normal stress also suppresses criticality in these systems. |
Wednesday, March 6, 2019 3:54PM - 4:06PM |
P65.00006: Mobility of Molecular Motors Regulates Contractile Behaviors of Actin Networks Atsushi Matsuda, Jing Li, Peter Brumm, Taiji Adachi, Yasuhiro Inoue, Taeyoon Kim Cells generate mechanical forces primarily from interactions between F-actin, cross-linking proteins, myosin motors, and other actin-binding proteins in the cytoskeleton. To understand how molecular interactions between the cytoskeletal elements generate forces, a number of in vitro experiments have been performed but are limited in their ability to accurately reproduce the diversity of motor mobility. In myosin motility assays, myosin heads are fixed on a surface and glide F-actin. By contrast, in reconstituted gels, the motion of myosin and F-actin are both unrestricted. Since only these two extreme conditions have been used, the importance of mobility of motors for network behaviors has remained unclear. In this study, to illuminate the impacts of motor mobility on the contractile behaviors of the actin cytoskeleton, we employed an agent-based computational model based on Brownian dynamics. We found that if motors can bind to only one F-actin like myosin I, networks are most contractile at intermediate mobility. On the contrary, if motors can bind to a pair of F-actins, a network can exhibit larger contraction with higher motor mobility. Results from this study imply that mobility of molecular motors may critically regulate contractile behaviors of actin networks in cells. |
Wednesday, March 6, 2019 4:06PM - 4:18PM |
P65.00007: Mechanical and Kinetic Factors Drive Sorting of Actin Crosslinkers Simon Freedman, Cristian Suarez, Jonathan Winkelman, David Kovar, Gregory A Voth, Aaron Dinner, Glen Hocky In cells, actin crosslinkers segregate to different cytoskeletal networks to perform distinct functions, such as forming filopodia to enable cell migration, or polarizing actin bundles to enable cell division. Recent experimental work revealed a passive mechanism that may control this spatial localization: the binding of a short crosslinker to two actin filaments can promote binding of other short crosslinkers and inhibit binding of longer crosslinkers. We hypothesize that this spatial localization is due to the fact that actin is semiflexible and cannot bend over short lengths. We develop a mathematical theory and a Monte Carlo simulation to elucidate the quantitative predictions of this hypothesis. Experiments confirm the predictions but reveal an unanticipated dependence of crosslinker domain size on the kinetics of actin filament polymerization and crosslinker binding affinity. We use simulations of a coarse-grained but molecularly explicit model to characterize the interplay of mechanical and kinetic parameters and understand the observed behavior. Our work demonstrates a physical mechanism by which cells can organize molecular material to drive biological processes, and it can guide the choice and/or design of crosslinkers for protein-based materials. |
Wednesday, March 6, 2019 4:18PM - 4:30PM |
P65.00008: Reconstitution of aster movement and cell division plane positioning mechanisms in Xenopus egg extract James Pelletier, Christine Field, Nikta Fakhri, John Oakey, Jay Gatlin, Timothy Mitchison During early development, microtubule asters move through the cytoplasm to position microtubule organizing centers (MTOCs) near the centers of subsequent cells. Aster movement is thought to depend on pulling forces by cytoplasmic dynein opposed by hydrodynamic drag; however, it remains unclear what are the cytoplasmic anchors, and how other cytoplasmic networks such as actin facilitate or hinder aster movement. We reconstituted aster growth, interaction, and movement in an actin-intact Xenopus egg extract system under quasi-2D confinement. We imaged microtubules, actin, and candidate cytoplasmic anchors. Asters interacted to generate dynamic Voronoi tessellations with edges corresponding to division planes. MTOCs moved toward the center of each polygon, mimicking their movement in vivo. Dynein inhibition blocked inward transport of cytoplasmic anchors. Actin depolymerization increased the rate of inward transport of anchors, but decreased the rate of aster movement. Actin depolymerized at Voronoi edges due to AurkB activity, resulting in aster movement away from edges. Our experiments inform how dynamic cytoplasmic networks interact to drive aster movement by dynein-dependent and -independent mechanisms. |
Wednesday, March 6, 2019 4:30PM - 4:42PM |
P65.00009: Chromatin Mechanics and the Biological Implication Yaojun Zhang, Daniel Lee, Yigal Meir, Cliff Brangwynne, Ned Wingreen The nucleus of the cell is a dense repository of information. But the DNA of the genome is more than just a string of letters – it forms “chromatin” a protein-nucleic-acid fiber with complex organization. Increasingly, the spatial organization of the genome has come into focus based on a suite of new technologies. The emerging picture spans scales from nucleosomes to loop domains to phase-separated regions. In parallel, the mechanics of chromatin has been probed by passive and active rheology, with its own emerging picture of chromatin as a viscoelastic and heterogeneous material. How are these two pictures related? To address this question, we developed a mechanistic model of chromatin using coarse-grained molecular dynamics simulations. The model captures chromatin’s central viscoelastic nature and its observed heterogeneity, and has revealed long-range cross-links as critical to reproduce experimental observations. Our results further elucidate the role of mechanics in fundamental biological processes taking place in the cell nucleus. |
Wednesday, March 6, 2019 4:42PM - 4:54PM |
P65.00010: Bacterial chromosome organization by collective dynamics of SMC condensins Christiaan A. Miermans, Chase P. Broedersz Recent Hi-C experiments of many bacterial species indicate a juxtaposed organization of the two chromosomal arms. These features in Hi-C maps have been attributed to various nucleoid-associated proteins, including the highly conserved SMC condensin. Although the molecular structure of these ATPases has been mapped in detail, it has been unclear how only a small number of condensins orchestrates this remarkable spatial organization. To resolve this puzzle, we developed a computational model for the dynamic organization of DNA by condensins as active slip-links. We first consider a scenario in which the ATPase activity of slip-links regulates their DNA-recruitment near the origin of replication, while the slip-link dynamics is assumed to be purely diffusive. We find that such diffusive slip-links can organize the entire chromosome into a state with aligned arms, but not within physiological constraints. However, slip-links that include motor activity are far more effective at organizing the entire chromosome, dynamically driving an entire chromosome into the juxtaposed state at physiological densities. We expand on these insights by showing the relation between this out-of-equilibrium organization and chromosome segregation. |
Wednesday, March 6, 2019 4:54PM - 5:06PM |
P65.00011: Ionic Conductance of 1.5 nm Diameter Carbon Nanotube Porins Aleksandr Noy Controlling ion transport on a molecular scale is important for applications ranging from industrial water treatment, to membrane separations, to bioelectronic interface design. Carbon nanotube porins—pore channels formed by ultra-short carbon nanotubes assembled in a lipid membrane—exploit nanoscale confinement and unique structure of carbon nanotube walls to transport water, protons, and small ions with efficiency that rivals and sometimes exceeds that of biological channels. We report the ion conductance characteristics and ion selectivity of the individual 1.5 nm dimeter carbon nanotube porins. The conductance follows the power law scaling that is distinct from the previously reported characteristics of carbon nanotubes. We will also discuss the physical mechanisms that lead to these conductance characteristics. Overall, carbon nanotube porins represent versatile biomimetic membrane pores that are ideal for studying nanoscale transport phenomena and building new separation technologies and bioelectronic interfaces. |
Wednesday, March 6, 2019 5:06PM - 5:18PM |
P65.00012: A Self-propelled Cruiser in 2D Granular Media under Gravity Guo-Jie Gao, Fu-Ling Yang We propose an extremely simple but efficient self-propelled cruiser, able to travel freely in 2D granular materials made of bidisperse dissipative particles under gravity. The cruiser has a round shape and a square indentation on its edge. To move into a given direction, perpendicular or parallel to gravity, we orient the indentation in line with the desired direction, and the cruiser shifts the granular particles entering its indent-region to its rear-half by a prescribed distance and then ejects them backward to gain thrust for moving forward. Using frictionless molecular dynamics (MD) method, we identify three universal phases of the cruiser during one particle-ejection process: 1) acceleration due to the ejection-thrust, 2) deceleration by the compressed particles ahead and 3) relaxation with the decompressed particles. We also confirm that the cruiser can travel continuously within the granular medium by successive particle-ejection, and the cruising performance increases with the ejection-strength and decreases by the interference from gravity. We believe our study demonstrates a novel approach to engineer self-propelled machines in granular materials. |
Wednesday, March 6, 2019 5:18PM - 5:30PM |
P65.00013: SOLUTION TO THE FOKKER-PLANCK EQUATION USING HOMOTOPIC TECHNIQUE Leonardo Apaza Pilco, Mario Sandoval-Espinoza We find the general solution to the Fokker-Planck equation using homotopic methods. This result is represented as a series solution in time. The series coefficients are determined as phase-space derivate operators. In addition, the general formalism is used to find mean values (variance and mean-square displacements) for the case of active Brownian particles on Euclidian and non-Euclidian spaces and under external fields. The theoretical results are validated using Brownian Dynamics simulations. |
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