Bulletin of the American Physical Society
APS March Meeting 2017
Volume 62, Number 4
Monday–Friday, March 13–17, 2017; New Orleans, Louisiana
Session C4: Physics of the Cytoskeleton IIFocus
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Sponsoring Units: DBIO GSOFT Chair: Jennifer Ross, University of Massachusetts Amherst Room: 263 |
Monday, March 13, 2017 2:30PM - 2:42PM |
C4.00001: Assembly and control of large microtubule complexes Kirill Korolev, Keisuke Ishihara, Timothy Mitchison Motility, division, and other cellular processes require rapid assembly and disassembly of microtubule structures. We report a new mechanism for the formation of asters, radial microtubule complexes found in very large cells. The standard model of aster growth assumes elongation of a fixed number of microtubules originating from the centrosomes. However, aster morphology in this model does not scale with cell size, and we found evidence for microtubule nucleation away from centrosomes. By combining polymerization dynamics and auto-catalytic nucleation of microtubules, we developed a new biophysical model of aster growth. The model predicts an explosive transition from an aster with a steady-state radius to one that expands as a travelling wave. At the transition, microtubule density increases continuously, but aster growth rate discontinuously jumps to a nonzero value. We tested our model with biochemical perturbations in egg extract and confirmed main theoretical predictions including the jump in the growth rate. Our results show that asters can grow even though individual microtubules are short and unstable. The dynamic balance between microtubule collapse and nucleation could be a general framework for the assembly and control of large microtubule complexes. [Preview Abstract] |
Monday, March 13, 2017 2:42PM - 2:54PM |
C4.00002: Characterizing active cytoskeletal dynamics with magnetic microposts Yu Shi, Steven Henry, John Crocker, Daniel Reich Characterization of an active matter system such as the cellular cytoskeleton requires knowledge of three frequency dependent quantities: the dynamic shear modulus, $G$*($\omega )$ describing its viscoelasticity, the Fourier power spectrum of forces in the material due to internal force generators $f(\omega )$, and the spectrum of the material's active strain fluctuations x($\omega )$. Via use of PDMS micropost arrays with magnetic nanowires embedded in selected posts, we measure the local complex modulus of cells through mechanical actuation of the magnetic microposts. The micrometer scale microposts are also used as passive probes to measure simultaneously the frequency dependent strain fluctuations. We present data on 3T3 fibroblasts, where we find power law behavior for both the frequency dependence of cells' modulus \textbar $G(\omega )$\textbar \textasciitilde $\omega^{\mathrm{0.27}}$ and the power spectrum of strain fluctuations \textbar x($\omega )$\textbar $\sim \omega^{\mathrm{-2}}$. Results for the power spectrum of active cytoskeletal stresses determined from these two measurements, and implications of this mesoscale characterization of cytoskeletal dynamics for cellular biophysics will also be discussed. [Preview Abstract] |
Monday, March 13, 2017 2:54PM - 3:06PM |
C4.00003: Emergent structures in simulations of cytoskeletal networks Simon Freedman, Shiladitya Banerjee, Glen Hocky, Aaron Dinner Within a cell, ensembles of cytoskeletal proteins with well understood microscopic interactions assemble into a wide variety of macroscopic structures that enable cell motility, division, and intracellular transport. We use our recently developed Active Filament Network Simulation (AFiNeS) software to explore the structure and dynamics of a minimal cytoskeletal system consisting of actin, crosslinkers, and myosin-II motors. By systematically varying the parameters of this model system, we find that we can tune between contractile networks which drive cell motility, bundled networks capable of propagating force large distances, and polarity sorted structures, which promote targeted intracellular transport. We show how these structures can emerge from varying both experimentally manipulatable parameters, such as myosin and crosslinker density, and varying parameters that are not readily accessible in experiments such as the affinity of a crosslinker to actin. These results can aid in understanding the stark mechanical diversity exhibited by cells with similar constituents, and the design of biomimetic active materials. [Preview Abstract] |
Monday, March 13, 2017 3:06PM - 3:42PM |
C4.00004: Mechanics of Active Matter Constructed from Actomyosin Invited Speaker: Margaret Gardel |
Monday, March 13, 2017 3:42PM - 3:54PM |
C4.00005: Active Alignment of Driven Copolymer Systems Leila Farhadi, Daniel Todd, Vikrant Yadav, Jennifer Ross Active matter spans length scales from macroscopic bird flocks to the sub-cellular microscale. The cytoskeleton is a model active network of filaments that exist in all cells, playing roles in many cell functions such as cell division, intracellular transport, and shaping the cell. Microtubules and actin are two cytoskeletal filaments that work together in cells to give shape and motility when combined with their accessory proteins and enzymes. Microtubules can be driven in filament gliding assays via kinesin-1 motor proteins. Actin filaments can be driven via myosin-II. Hydrolysis of ATP is the energy source for the movement of these motor driven filaments in the cell to perform their function. Prior work has studied each of these filaments and their associate motors individually, we are interested to study both of them together in an in vitro motility assay. This is interesting because their stiffnesses vary by several orders of magnitude, with actin being floppier $(L_p \sim 16 \mu m)$ and microtubules being stiffer $(L_p \sim 1 mm)$. We explore different patterns formed by actin and microtubule filaments above certain concentration where non-equilibrium disordered to ordered transition of filament takes place. [Preview Abstract] |
Monday, March 13, 2017 3:54PM - 4:06PM |
C4.00006: Tunable deformation modes shape contractility in active biopolymer networks Samantha Stam, Shiladitya Banerjee, Kim Weirich, Simon Freedman, Aaron Dinner, Margaret Gardel Biological polymer-based materials remodel under active, molecular motor-driven forces to perform diverse physiological roles, such as force transmission and spatial self-organization. Critical to understanding these biomaterials is elucidating the role of microscopic polymer deformations, such as stretching, bending, buckling, and relative sliding, on material remodeling. Here, we report that the shape of motor-driven deformations can be used to identify microscopic deformation modes and determine how they propagate to longer length scales. In cross-linked actin networks with sufficiently low densities of the motor protein myosin II, microscopic network deformations are predominantly uniaxial, or dominated by sliding. However, longer-wavelength modes are mostly biaxial, or dominated by bending and buckling, indicating that deformations with uniaxial shapes do not propagate across length scales significantly larger than that of individual polymers. As the density of myosin II is increased, biaxial modes dominate on all length scales we examine due to buildup of sufficient stress to produce smaller-wavelength buckling. In contrast, when we construct networks from unipolar, rigid actin bundles, we observe uniaxial, sliding-based contractions on 1 to 100 $\mu $m length scales. Our results demonstrate the biopolymer mechanics can be used to tune deformation modes which, in turn, control shape changes in active materials. [Preview Abstract] |
Monday, March 13, 2017 4:06PM - 4:18PM |
C4.00007: Tunable Magnetic Forces for Trajectory Modification of Gliding Microtubules G.B. Vieira, K.D. Mahajan, G. Ruan, C.J. Dorcena, G. Nabar, N.F. Bouxsein, J.J. Chalmers, G.D. Bachand, R. Sooryakumar, J.O. Winter Carefully engineering patterned magnetic structures provides the ability to apply directed, tunable forces to nanoscale fluid-borne objects due to the presence of localized magnetic field gradients. Here we apply this technique to investigate dynamic control of the motion of the ATP-driven microtubules (MTs) gliding on a kinesin-coated surface. The MTs are combined with magnetic nanoparticles and quantum dots to facilitate application of forces and fluorescent tracking. We observe that MTs can be deflected or trapped by the magnetic structures while the ATP-driven motion persists. This manipulation technology may be ideal for biological systems and biomedical applications because directional changes in motor-based transport are induced non-invasively, and the technique can be scaled up to apply forces at many locations simultaneously on the same device. [Preview Abstract] |
Monday, March 13, 2017 4:18PM - 4:30PM |
C4.00008: Effect of membrane coupling on multiple-kinesin transport Joseph Lopes, Dail Chapman, Linda Hirst, Jing Xu Molecular motor-based transport is critical for all eukaryotic cell function and health. Although traditionally examined in the context of single motor experiments, molecular motors often work in small teams together to transport the same cargo in vivo. Factors that control and regulate the group function of multiple motors has remained unclear. Here we used a simple lipid bilayer to couple kinesin motors together, and used microtubule gliding assay to examine the effect of this membrane coupling on the group function of multiple kinesin motors. [Preview Abstract] |
Monday, March 13, 2017 4:30PM - 4:42PM |
C4.00009: Modeling motor-driven cargo transport in cytoskeletal networks Kevin Ching, Supravat Dey, Moumita Das Intracellular transport of organelles, vesicles, and other cargo by molecular motors is essential to proper functioning of cells. Most models of cargo transport have focused on the dilute limit of a single motor moving along a single filament. In cells, however, motors transporting cargos have to navigate crowded, space filling networks. Furthermore, cargos are rarely carried by a single motor, and motor-motor interactions may occur during collective transport of cargos. Motivated by this, we mathematically model the transport of cargo – motor complex in filamentous networks, using a combination of analytical calculations and numerical simulations. We study cargo MSDs, and velocities as functions of mechanical properties of the cargo and the network, as well as motor density, and motor-motor interactions. Our results may help to understand how multiple motors transport large cargos in the cytoskeletal network. [Preview Abstract] |
Monday, March 13, 2017 4:42PM - 4:54PM |
C4.00010: Analysis of Intracellular Transport by Teams of Molecular Motors Shreyas Bhaban, Saurav Talukdar, Donatello Materassi, Mingang Li, Thomas Hays, Murti Salapaka Intracellular transport of cargoes, such as organelles, are enabled by nano-scale bio-mechanical agents called 'motor proteins', which attach to the cargo and transport it to their destination by 'walking' over filaments. The motors carry cargoes against load forces that are less than their characteristic 'stalling force'. Often transport is mediated by teams of motors, possibly of the same or different types. We develop a semi-analytical method to analyze the emergent transport properties of motor ensembles, by investigating the relative arrangements of motors while carrying a cargo. Study reveals that the relative configurations approach a unique steady state distribution, enforcing the robustness of the motor-cargo assembly. As the load on the cargo increases, motors tend to cluster together. Under high loads, akin to sudden obstacles, motors assume configurations that favor immediate cargo translocation when the load eventually subsides. Furthermore, participation by motors with varying stall forces reveals surprising results. Results indicate that a minority of motors with altered stall forces can determine average run-length and velocity of the cargo. Such mutations are related to neurological disorders, providing a potential insight into the onset of neuro-degeneration. [Preview Abstract] |
Monday, March 13, 2017 4:54PM - 5:06PM |
C4.00011: Intracellular Transport of Cargo in a Sub-diffusive Environment over an Explicit Cytoskeletal Network Bryan Maelfeyt, Ajay Gopinathan Intracellular transport occurs in nearly all eukaryotic cells, where materials such as proteins, lipids, carbohydrates, and nucleic acids travel to target locations through phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton.We develop a computational model of the process with explicit cytoskeletal filament networks. In the active transport phase, cargo moves in straight lines along these filaments that are spread throughout the cell. To model the passive transport phase of cargo in the cytoplasm, where anomalous sub-diffusion is thought to take place, we implement a continuous-time random walk. We use this approach to provide a stepping stone to a predictive model where we can determine transport properties over a cytoskeletal network provided by experimental images of real filaments. We illustrate our approach by modeling the transport of insulin out of the cell and determining the impact of network geometry, anomalous sub-diffusion and motor number on the first-passage time distributions for insulin granules reaching their target destinations on the membrane. [Preview Abstract] |
Monday, March 13, 2017 5:06PM - 5:18PM |
C4.00012: The statistics of molecular motor trajectories on different two-dimensional structures S. M. Ali Tabei, Faezeh Jahanmiri-Nezhad, Michael Martin, Colten Lastine Molecular motors move on a complex cytoskeleton network to transport material within the cell. In this talk, we investigate different scenarios of transport on two-dimensional network structures. We will study different statistical properties of an ensemble of simulated trajectories such as the frequency of directional changes and diffusion statistics. We will investigate how these statistical measures depend on the geometrical properties of the underlying structure. [Preview Abstract] |
Monday, March 13, 2017 5:18PM - 5:30PM |
C4.00013: Anomalously slow transport of large particles inside microtubules due to slow binding Andrew Rutenberg, Spencer Farrell Bulk and single-particle mobilities are equal in single-file diffusion without bound immobile particles, or when the binding kinetics are sufficiently fast. However, using stochastic simulations we have found that for slow binding kinetics there is strong anomalous slowing that depends on both binding and unbinding rates. This effect, which requires finite particle density, is distinct from the well understood density-dependent tracer-particle diffusion seen in single-file diffusion without binding. We find strong slowing in the parameter regime expected for luminal diffusion of the acetylation enzyme $\alpha$TAT1 within microtubules. We also present a scaling argument for the reduced transport at moderate to high densities that captures the observed slowing. [Preview Abstract] |
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