Bulletin of the American Physical Society
APS March Meeting 2022
Volume 67, Number 3
Monday–Friday, March 14–18, 2022; Chicago
Session S07: Mechanics of Cells and Tissues: The Role of Heterogeneity IFocus Recordings Available
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Sponsoring Units: DBIO GSNP DSOFT Chair: Jonathan Michel, Rochester Institute of Technology Room: McCormick Place W-179A |
Thursday, March 17, 2022 8:00AM - 8:12AM |
S07.00001: Lack of Neighbor Exchanges From Modulating Epithelial Cell Movement Through Division and Substrate Stiffness Ayanna Matthews, Margaret Gardel, Sidney R Nagel Control over multicellular tissue has implications for morphogenesis, tissue repair, and disease progression. However, how the architecture and dynamics of multicellular tissue is controlled is largely unknown. Key to this control is cell-generated active stress which drives cell movement and shape change. Until recently, it was believed that the dominant stresses driving cell locomotion arise from substrate interactions involving focal-adhesion signaling with the extracellular matrix. However, recent work demonstrated that, under conditions with minimal focal-adhesion signaling, the cell cycle drives fluctuations at cell-cell interfaces. We explore the interplay between these two origins of active stress in epithelia by using cells whose cell cycle is stalled and by modifying the extracellular matrix to which the model tissue is attached. Intriguingly, we find that the cell cycle-dependent stresses generate large fluctuations of cell shape, but negligible cell-neighbor exchanges. Through varying culture conditions which modulate epithelial cell motility, we find little evidence of fluid-like states as suggested by the Vertex Model, a prevailing model for epithelial tissue dynamics. We explore instead other possible models to understand the full range of the experimental data. |
Thursday, March 17, 2022 8:12AM - 8:24AM |
S07.00002: Effect of compression on tumor fluidity and invasion. Mrinal Pandey, Young Joon Suh, Minha Kim, Hannah J Davis, Jeffrey E Segall, Mingming Wu Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stresses within the tumor. In this study, we developed a 3D in vitro model to study tumor spheroids under mechanical compression. Breast tumor spheroids of MDA-MB-231 cells were prepared and suspended in a dense 3D collagen matrix. A constant compressive load was then applied to them. The dynamics of tumor spheroids and cells within the spheroid were imaged and analyzed. Spheroid morphology and single-cell motility parameters were studied. We found that the spheroids under compression exhibit more dynamic shape changes in contrast to control. More importantly, compression promoted tumor invasion. |
Thursday, March 17, 2022 8:24AM - 8:36AM |
S07.00003: Rheology of the cellular vertex model with external and internal dissipation Sijie Tong, Rastko Sknepnek, Andrej Kosmrlj Complex rheological properties of epithelia are the result of tissue’s ability to actively tune viscoelastic interactions between its constituent cells. While numerous studies have revealed emergent rheological properties of epithelial tissues by measuring the response to various kinds of mechanical deformations, less is known about the role played by different cellular mechanisms of dissipation. The cell-based vertex model has been widely used to describe the mechanical properties of epithelia. Most studies, however, use a simplified dissipative model with friction only due to the interaction between cells and the substrate. Our recent work [1] has shown that the linear viscoelastic properties of the vertex model with cell-substrate dissipation can be mapped to standard spring-dashpot models. Here, we show that extending the model to include dissipation due to relative motion of cells with respect to each other has non-trivial effects on rheology in the linear regime. We achieve this by combining vertex model simulations for both ordered and disordered configurations with semi-analytical calculations that offer an efficient tool to understand the rheological properties of epithelia. |
Thursday, March 17, 2022 8:36AM - 9:12AM |
S07.00004: Vimentin intermediate filament networks are required for compression stiffening of cells and protection of nuclei from compressive stress. Invited Speaker: Paul Janmey The semi-flexible polymer networks that form the cytoskeleton are heterogeneously distributed and are regulated by different molecular mechanisms. In mesenchymal cells, the intermediate filament network formed by vimentin is concentrated near the nucleus, although it also makes some contacts with the actin-rich cell cortex. The physical properties of the three cytoskeletal filaments and the networks they form are also distinct, especially in uniaxial deformation. Rigid and semi-flexible biopolymer networks generally stiffen when deformed in shear but soften in compression due to filament buckling. However, unlike crosslinked networks of purified F-actin or microtubules, which soften in compression, vimentin intermediate filament networks stiffen in both compression and extension by a mechanism that involves the greater flexibility of vimentin and the large surface charge of the vimentin filament that resists volume changes under compression. Individual cells, such as fibroblasts, stiffen at physiologically relevant compressive strains, but deletion of vimentin diminishes this effect. Vimentin null fibroblasts suffer greater damage to the nucleus after cell compression than normal cells. These results provide a new framework by which to understand the mechanical responses of cells and point to a central role of intermediate filaments in response to compression |
Thursday, March 17, 2022 9:12AM - 9:24AM Withdrawn |
S07.00005: Nanofibril-mediated Hierarchical Fracture Resistance of Bone Ottman A Tertuliano Natural hard composites like human bone possess a combination of strength and toughness that exceeds that of their constituents and of many engineered composites. This augmentation is attributed to their complex hierarchical structure, spanning multiple length scales; in bone, characteristic dimensions range from nanoscale fibrils to microscale lamellae to mesoscale osteons and macroscale organs. The mechanical properties of bone have been studied, with the understanding that the isolated microstructure at micro- and nano-scales gives rise to superior strength compared to that of whole tissue, and the tissue possesses an amplified toughness relative to that of its nanoscale constituents. Nanoscale toughening mechanisms of bone are not adequately understood at sample dimensions that allow for isolating salient microstructural features, because of the challenge of performing fracture experiments on small-sized samples. We developed an in situ three-point bend experimental methodology that probes site-specific fracture behavior of micron-sized specimens of hard material. Using this, we quantify crack initiation and growth toughness of human trabecular bone with sharp fatigue pre-cracks and blunt notches. Our findings indicate that bone with fatigue cracks is two times tougher than that with blunt cracks. In situ data-correlated electron microscopy videos reveal this behavior arises from crack-bridging by nanoscale fibril structure. The results reveal a transition between fibril-bridging (∼1 μm) and crack deflection/twist (∼500 μm) as a function of length-scale, and quantitatively demonstrate hierarchy-induced toughening in a complex material. This versatile approach enables quantifying the relationship between toughness and microstructure in various complex material systems and provides direct insight for designing biomimetic composites. |
Thursday, March 17, 2022 9:24AM - 9:36AM |
S07.00006: Microstructure-Based Constitutive Model of Nuclear Lamina Networks Nima Mostafazadeh Nuclear lamina networks in mammalian somatic cells consist of irregularly orientated lamin filaments with varying initial lengths. In this study, we developed a microstructure-based model of lamina networks with orientation and initial length distributions of lamin filaments obtained from experimental imaging. We first established a theoretical force-extension model of lamin filaments including domain unfolding based on the steered molecular dynamics simulations and AFM stretching experiments. Using this force-extension model, we then derived the stresses of the microstructure-based model of lamina networks under large deformation. For the first time, we also derived the elasticity tensor of general two-dimensional hyperelastic networks, which can be used for calculating the consistent tangent matrix in the finite element formulation. To validate our microstructure-based lamina model, we first apply it to simulate the micropipette aspiration of isolated nuclei and compare the aspiration length with experimental data. We also validated our model against AFM indentation experiments. Finally, we simulated the nucleus passing through the constriction of inter-endothelial pores and compared the resistance force and deformation with an existing study. We investigated the differences between our microstructure-based model and empirical hyperelastic models such as neo-Hookean used in the existing studies. Our new model paves the road for quantitative understanding of rupture and mechanosensation of nuclear enveloples. |
Thursday, March 17, 2022 9:36AM - 9:48AM |
S07.00007: E2 and Gamma Distributions in Polygonal Networks Ran Li, Hao Lin, Seyedsajad Moazzeni, Zhenru Zhou, Kenneth Irvine, Consuelo Ibar, Liping Liu, Andrew N. Norris From solar supergranulation to salt flats in Bolivia, from veins on leaves to cells on Drosophila wing disks, polygon-based networks exhibit great complexities, yet similarities and consistent patterns emerge. Based on analysis of 99 polygonal tessellations with a wide variety of physical origins, this work demonstrates the ubiquity of an exponential distribution in the squared norm of the deformation tensor E2, which directly leads to the ubiquitous presence of gamma distributions in the polygon aspect ratio, as recently demonstrated by Atia et al. [Nat. Phys. 14, 613 (2018)]. In turn an analytical approach is developed to illustrate its origin. E2 relates to most energy forms, and its Boltzmann-like feature allows the definition of a pseudo temperature that promises utility in a thermodynamic ensemble framework. |
Thursday, March 17, 2022 9:48AM - 10:00AM |
S07.00008: Reentrant Rigidity Percolation in Correlated Elastic Networks Jonathan A Michel, Thomas S Wyse Jackson, Gabriel von Kessel, Lawrence Bonassar, Itai Cohen, Moumita Das Tissues made of semiflexible biopolymers are often modeled as a dilute network of fibers that resist bending and stretching, with the network elastic moduli depending critically on the fraction of bonds. While homogenous dilution is applicable for some biopolymer networks, our interest in networks with pronounced spatial variations, such as collagen in articular cartilage, motivates a network construction protocol that produces structural correlation. We model structurally correlated, dilute Kagome lattice-based networks and compute their linear response to simple shear. We find that the threshold bond fraction needed to produce a rigid network nonmonotonically depends on the structural correlation, with a global minimum for an optimal correlation strength. We also find a mechanical length scale, inferred from correlations in non-affine deformation, that grows monotonically with correlation. This suggests the reentrance of rigidity percolation arises from a weak coupling between large, stiff domains. We further discuss extending our model to address composite tissues by coupling our correlated networks to a continuous elastic background. |
Thursday, March 17, 2022 10:00AM - 10:12AM |
S07.00009: Cells-ECM mechanical interaction: taking advantage of nonlinearities for mechanosensing. Estelle Berthier, Pierre Ronceray, Chase P Broedersz Most viable cells are anchored to the extracellular matrix (ECM) and can detect its rigidity by mechanically probing the network (mechanosensing). However, the ECM is a highly heterogeneous structure with large mechanical fluctuations: the local stiffness exhibits a broad distribution. Yet, cells respond robustly to the mechanical cues of the ECM and adequately regulate their behavior. Hence, it remains unclear what strategies cells employ to accurately interpret mechanical guiding cues of such a heterogeneous environment. |
Thursday, March 17, 2022 10:12AM - 10:24AM |
S07.00010: A Tensegrity Framework to Study Force Balance in Tissues Allyson Q Ryan, Carl D Modes Redistribution of applied forces in biological tissues is critical to both function and damage prevention. Mechanistic understanding of force balance in individual tissues is somewhat lacking. In many cases this is due to tissue inaccessibility, which eliminates the possibility to probe material properties and responses in situ. Dural reflections, part of the outermost meningeal layer, are responsible for maintaining the position of and divisions between brain lobes. Though evidently a key function, how reflections balance applied forces, both acute and chronic, in the cranium is unknown. We have therefore chosen to build a tensegrity framework through which unperturbed prestressed states as well as applied force conditions can be investigated in silico. Tensegrities are comprised of a continuous tensile network with interspersed compression-bearing elements and offer the possibility to study the geometric maintenance and deformation of tissues in various states. Here we present a tensegrity system of the largest reflection, the Falx cerebri, which sits between the left and right hemispheres of the cerebrum. By modelling the Falx as an elastic sheet under tension with boundaries under either tension or compression, we explore the distribution of stress over the tissue and the range of applied force over which geometric integrity is maintained. |
Thursday, March 17, 2022 10:24AM - 10:36AM Withdrawn |
S07.00011: Nuclear membrane three orders magnitude faster Kisung Lee, Sun-Min Yu, Steve Granick We detect fluctuations of cell nucleus envelope over the exceptionally broad spatiotemporal resolution. The frequency range of 0.1 to 1,000 Hz with an amplitude resolution of nm reveals surprises regarding underlying processes occurring in the membrane. |
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