Bulletin of the American Physical Society
APS March Meeting 2017
Volume 62, Number 4
Monday–Friday, March 13–17, 2017; New Orleans, Louisiana
Session E6: Cell and Tissue Mechanics |
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Sponsoring Units: DBIO GSOFT Chair: Vernita Gordon, University of Texas Room: 265 |
Tuesday, March 14, 2017 8:00AM - 8:12AM |
E6.00001: Finite-deformation mechanics of generalized cell vertex models Tristan Sharp, Matthias Merkel, Lisa Manning, Andrea Liu A class of models called cell vertex models has been shown to capture aspects of the mechanics of confluent cell tissues (tissues in which constituent cells occupy essentially all of the volume). We investigate the mechanics of a cell vertex model beyond the regime of linear response, in 2D and 3D. In such tissues, we assume an energy cost for cell deformations that arises when cells are locally compressed together. We introduce a generalization of a cell vertex model to include key effects of the extracellular matrix (ECM) in non-confluent biological tissues. Because the ECM can prevent rearrangements in which cells change neighbors, we also introduce an energy penalty to suppress rearrangements. We describe the consequences of these added interactions on the rigidity transition and nonlinear mechanics. [Preview Abstract] |
Tuesday, March 14, 2017 8:12AM - 8:24AM |
E6.00002: A theoretical and computational framework for mechanics of the cortex Alejandro Torres-Sánchez, Marino Arroyo The cell cortex is a thin network of actin filaments lying beneath the cell surface of animal cells. Myosin motors exert contractile forces in this network leading to active stresses, which play a key role in processes such as cytokinesis or cell migration. Thus, understanding the mechanics of the cortex is fundamental to understand the mechanics of animal cells. Due to the dynamic remodeling of the actin network, the cortex behaves as a viscoelastic fluid. Furthermore, due to the difference between its thickness (tens of nanometers) and its dimensions (tens of microns), the cortex can be regarded a surface. Thus, we can model the cortex as a viscoelastic fluid, confined to a surface, that generates active stresses. Interestingly, geometric confinement results in the coupling between shape generation and material flows. In this work we present a theoretical framework to model the mechanics of the cortex that couples elasticity, hydrodynamics and force generation. We complement our theoretical description with a computational setting to simulate the resulting non-linear equations. We use this methodology to understand different processes such as asymmetric cell division or experimental probing of the rheology of the cortex [Preview Abstract] |
Tuesday, March 14, 2017 8:24AM - 8:36AM |
E6.00003: ECM remodeling and its plasticity Jingchen Feng, Christopher A. R Jones, Matthew Cibula, Xiaoming Mao, Leonard M. Sander, Herbert Levine, Bo Sun The mechanical interactions between cells and Extracellular Matrix (ECM) are of great importance in many cellular processes. These interactions are reciprocal, i.e. contracting cells pull and reorganize the surrounding matrix, while the remodeled matrix feeds back to regulate cell activities. Recent experiments show in collagen gels with densely distributed cells, aligned fiber bundles are formed in the direction between neighboring cells. Fibers flow into the center region between contracting cell pairs in this process, which causes the concentration of fibers in the fiber bundles to become significantly enhanced. Using an extended lattice-based model, we show that viscoelasticity plays an essential role in ECM remodeling and contributes to the enhanced concentration in fiber bundles. We further characterize ECM plasticity within our model and verify our results with rheometer experiments. [Preview Abstract] |
Tuesday, March 14, 2017 8:36AM - 8:48AM |
E6.00004: Mitochondrial fluctuations as a measure of active biomechanical properties of mammalian cells Wenlong Xu, Elaheh Alizadeh, Jordan Castle, Ashok Prasad A single-cell assay of mechanical properties would give significant insights into cellular processes. Force spectrum microscopy is one such technique, which involves both active and passive particle tracking microrheology on the same cells. Since active microrheology requires expensive instruments, it is of great interest to develop simpler alternatives. Here we study an alternative using endogenous mitochondrial fluctuations, rather than fluorescent beads, in particle tracking microrheology. Mitochondria of the C3H-10T1/2 cell line are labeled and tracked using confocal microscopy, their mean square displacement (MSD) measured, and mechanical parameters calculated. Active fluctuations are distinguished from passive fluctuations by treatment with ATP synthesis inhibitors. We find that the MSD of mitochondria resembles that of particles in viscoelastic media. However, comparisons of MSD between controls and cells disrupted in the actin or microtubule network showed surprisingly small effects, while ATP-depleted cells showed significantly decreased MSD, and characteristics of thermally driven fluctuations. Both active and ATP-depleted parameters showed heterogeneity among cells and between cell lines. This method is potentially very useful due to its simplicity. [Preview Abstract] |
Tuesday, March 14, 2017 8:48AM - 9:00AM |
E6.00005: Force fluctuations of non-adherent cells: effects of osmotic pressure and motor inhibition Samaneh Rezvani, Christoph F. Schmidt, Todd M. Squires Cells sense their micro-environment through biochemical and mechanical interactions. They can respond to stimuli by undergoing shape- and possibly volume changes. Key components in determining the mechanical response of a cell are the viscoelastic properties of the actomyosin cortex, effective surface tension, and the osmotic pressure. We use custom-designed microfluidic chambers with integrated hydrogel micro windows to be able to rapidly change solution conditions for cells without active mixing, stirring or diluting of fluid. We use biochemical inhibitors and different osmolytes and investigate the time-dependent response of individual cells. Using a dual optical trap makes it possible to probe viscoelasticity of suspended cells by active and passive microrheology to quantify the response to the various stimuli. [Preview Abstract] |
Tuesday, March 14, 2017 9:00AM - 9:12AM |
E6.00006: Mechanical response and buckling of a polymer simulation model of the cell nucleus Edward Banigan, Andrew Stephens, John Marko The cell nucleus must robustly resist extra- and intracellular forces to maintain genome architecture. Micromanipulation experiments measuring nuclear mechanical response reveal that the nucleus has two force response regimes: a linear short-extension response due to the chromatin interior and a stiffer long-extension response from lamin A, comprising the intermediate filament protein shell. To explain these results, we developed a quantitative simulation model with realistic parameters for chromatin and the lamina. Our model predicts that crosslinking between chromatin and the lamina is essential for responding to small strains and that changes to the interior topological organization can alter the mechanical response of the whole nucleus. Thus, chromatin polymer elasticity, not osmotic pressure, is the dominant regulator of this force response. Our model reveals a novel buckling transition for polymer shells: as force increases, the shell buckles transverse to the applied force. This transition, which arises from topological constrains in the lamina, can be mitigated by tuning the properties of the chromatin interior. Thus, we find that the genome is a resistive mechanical element that can be tuned by its organization and connectivity to the lamina. [Preview Abstract] |
Tuesday, March 14, 2017 9:12AM - 9:24AM |
E6.00007: Disentangle Viscoelasticity on Primary Plant Cell Walls Jacob Seifert, Ian Moore, Sonia Contera The mechanics of plant growth, the ultimate result of plant development, is primarily determined by the mechanical properties of the primary cell wall (CW). This CW is an intricate composite material made from a compliant matrix and a fiber network. The mechanics of cells can be measured elastically and viscoelastically by quasi-static and dynamic, such as contact-resonance and multi-frequency, atomic force microscopy (AFM) techniques. While the quasi-static measurements already found application on living plant tissues, viscoelastic measurements give the dynamic component which is important for growth. They have been, however, only applied to isolated animal and bacterial cells using the Kelvin-Voigt model, so far. Here, we applied dynamic AFM methods to measure the viscoelastic properties on living plant tissues and extended the model to the linear standard solid model, which is more appropriate for polymeric materials, and gives quantitative information about the viscoelastic response time. Furthermore, we show that an alteration of the plant cell wall material composition and organization by chemical treatment can be mapped using dynamic AFM methods to spatially display a change of the material and disentangle results previously found from quasi-static measurements. [Preview Abstract] |
Tuesday, March 14, 2017 9:24AM - 9:36AM |
E6.00008: Physical limits to biomechanical sensing in disordered fiber networks Farzan Beroz, Louise Jawerth, Stefan Münster, David Weitz, Chase Broedersz, Ned Wingreen Cells actively probe and respond to the stiffness of their surroundings. Since mechanosensory cells in connective tissue are surrounded by a disordered network of biopolymers, their mechanical environment can be extremely heterogeneous. Here, we investigate how this heterogeneity impacts mechanosensing by modeling the cell as an idealized local stiffness sensor inside a disordered fiber network. For all types of networks we study, including experimentally-imaged collagen and fibrin architectures, we find that measurements applied at different points yield a strikingly broad range of local stiffnesses, spanning roughly two decades. We verify via simulations and scaling arguments that this broad range of local stiffnesses is a generic property of disordered fiber networks. Finally, we show that to obtain optimal, reliable estimates of global tissue stiffness, a cell must adjust its size, shape, and position to integrate multiple stiffness measurements over extended regions of space. [Preview Abstract] |
Tuesday, March 14, 2017 9:36AM - 9:48AM |
E6.00009: Emergent versus Individual-based Chemotaxis in Cell Clusters Julien Varennes, Sean Fancher, Hye-ran Moon, Bumsoo Han, Andrew Mugler Sensing and migration occur in development, morphogenesis, cancer metastasis, and countless other multicellular processes. Although collective cell sensing and migration have been studied in the context of many different biological systems, universal limits to the precision of the different collective migratory mechanisms observed have yet to be quantified. Here we develop and compare two model forms of collective sensing and migration: one in which cells individually choose their polarization direction (“individual-based” chemotaxis), and the other in which collective migration emerges from intercellular interactions within the cluster (“emergent” chemotaxis). The limits to the migratory precision of these two classes of collective migration are presented. We show how the chemotactic index (CI) and chemotactic ratio (CR) are simple functions of migratory precision giving us predictive power on how CI and CR depend on system parameters such as chemical concentration, gradient, and cell cluster size. Ongoing cell migration experiments to test these predictions are discussed. [Preview Abstract] |
Tuesday, March 14, 2017 9:48AM - 10:00AM |
E6.00010: Physical mechanisms of collective expansion in confluent tissues in an Active Vertex Model Michael Czajkowski, Dapeng Bi, Xingbo Yang, Matthias Merkel, M. Lisa Manning, M. Cristina Marchetti Living tissues form many novel patterns due to the active forces exerted by the constituent cells. How these forces combine with proliferation (changing number density) and boundary conditions to control the resultant patterns is an interesting open question. This question arises naturally for in vitro wound healing experiments, where an initially confined monolayer is allowed to expand freely. As the cells interact, proliferate and advance laterally, a characteristic pattern of traction stresses is formed on the substrate. We have developed an Active Vertex Model to make predictions about active confluent tissues with free boundaries. The model incorporates active forces, flocking interactions, and simple rules for cell division within the vertex model geometry. It also exhibits a fluid-solid transition, with qualitatively distinct stress profiles in the solid and in the liquid. Furthermore, under the assumption that cells proliferate more when stretched, we find that polar alignment interactions strongly enhance cell proliferation. Our model suggests that wound healing assays may provide a useful rheological tool for tissues, as well as a novel system for studying the connection between proliferation and flocking. [Preview Abstract] |
Tuesday, March 14, 2017 10:00AM - 10:12AM |
E6.00011: Overcrowding drives the unjamming transition of gap-free monolayers Ganhui Lan, Tao Su Collective cell motility plays central roles in various biological phenomena such as wound healing, cancer metastasis and embryogenesis. These are demonstrations of the unjamming transition in biology. However, contradictory to the typical density-driven jamming in particulate assemblies, cellular systems often get unjammed in highly packed, sometimes overcrowding environments. Here, we investigate monolayers' collective behaviors when cell number changes under the gap-free constraint. We report that overcrowding can unjam gap-free monolayers through increasing isotropic compression. We show that the transition boundary is determined by the isotropic compression and the cell-cell adhesion. Furthermore, we construct the free energy landscape for the T1 topological transition during monolayer rearrangement, and discover that the landscape evolves from single-barrier W shape to double-barrier M shape during the unjamming process. We also discover a distributed-to-disordered morphological transition of cells' geometry, coinciding with the unjamming transition. Our analyses reveal that the overcrowding and adhesion induced unjamming reflects the mechanical yielding of the highly deformable monolayer, suggesting an alternative mechanism that cells may robustly gain collective mobility through proliferation in confined environments, which differs from those caused by loosing up a packed particulate assembly. [Preview Abstract] |
Tuesday, March 14, 2017 10:12AM - 10:24AM |
E6.00012: A rigidity transition and glassy dynamics in a model for confluent 3D tissues Matthias Merkel, M. Lisa Manning The origin of rigidity in disordered materials is an outstanding open problem in statistical physics. Recently, a new type of rigidity transition was discovered in a family of models for 2D biological tissues, but the mechanisms responsible for rigidity remain unclear. This is not just a statistical physics problem, but also relevant for embryonic development, cancer growth, and wound healing. To gain insight into this rigidity transition and make new predictions about biological bulk tissues, we have developed a fully 3D self-propelled Voronoi (SPV) model. The model takes into account shape, elasticity, and self-propelled motion of the individual cells. We find that in the absence of self-propulsion, this model exhibits a rigidity transition that is controlled by a dimensionless model parameter describing the preferred cell shape, with an accompanying structural order parameter. In the presence of self-propulsion, the rigidity transition appears as a glass-like transition featuring caging and aging effects. Given the similarities between this transition and jamming in particulate solids, it is natural to ask if the two transitions are related. By comparing statistics of Voronoi geometries, we show the transitions are surprisingly close but demonstrably distinct. Furthermore, an index theorem used to identify topologically protected mechanical modes in jammed systems can be extended to these vertex-type models. In our model, residual stresses govern the transition and enter the index theorem in a different way compared to jammed particles, suggesting the origin of rigidity may be different between the two. [Preview Abstract] |
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