Bulletin of the American Physical Society
APS March Meeting 2021
Volume 66, Number 1
Monday–Friday, March 15–19, 2021; Virtual; Time Zone: Central Daylight Time, USA
Session B11: Mechanics of Cells and Tissues IIFocus Session Live
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Sponsoring Units: DBIO Chair: Daniel Cohen, Princeton University; Ming Ming Wu, Cornell University |
Monday, March 15, 2021 11:30AM - 11:42AM Live |
B11.00001: Developing epithelial tissues as active materials: Tracking cell dynamics in dorsal closure using machine learning Daniel Haertter, Stephanie Fogerson, Janice Crawford, Daniel P. Kiehart, Christoph F. Schmidt Dorsal closure in Drosophila melanogaster embryos is a key model system for cell sheet morphogenesis and wound healing. Understanding system dynamics, regulation and causal relations requires a quantitative understanding of the mesoscopic mechanical and dynamic properties of this “active soft material”. We utilized deep learning to automatically and robustly detect and temporally track various features, even in noisy microscopy movies: individual cell shapes in two distinct tissue types, cell junctions and edge lengths, and tissue topology. Past studies of epithelial dynamics were restricted to semi-manual segmentation of cell shapes and thus suffered from relatively low statistics. Our automatized algorithm reduces processing time for 1000 frames from weeks to 20 min and allows us to harvest high-quality temporal data from ~1000 cells per embryo. Epithelial cells in dorsal closure exhibit oscillations and contribute to progressive cell sheet movements, while showing a large variability in individual shapes and dynamics. Using spatial and temporal correlations and unsupervised machine learning techniques, we detect subtle behavioral phenotypes and emerging dynamical pattern on basis of the cell’s high-dimensional features. |
Monday, March 15, 2021 11:42AM - 11:54AM Live |
B11.00002: Emergent multi-cellular network structures due to mechanical interactions Patrick Noerr, Farnaz Golnaraghi, Ajay Gopinathan, Kinjal Dasbiswas Cells probe their local environment by exerting forces on elastic extracellular substrates. Due to mechanical interactions that arise from mutual deformations of the substrate, neighboring cells may align into elongated structures such as chains and rings. The formation of rings of cells are the basis of biological structures such as blood vessels. Using an agent-based model of adherent elastically interacting cells, we explore structure formation in multicellular assemblies on a soft substrate by using quantitative metrics such as percolation, number of junctions, branch length, and orientational order to make structure predictions as a function of mechanical characteristics including compressibility and rigidity. Combining these elastically interacting cells with self-propulsion constitutes a new type of active matter. Unlike traditional active particles, cells can self-regulate behavior based on environmental factors, such as neighboring cell proximity and prestrain, thus exhibiting adaptive motility. Applications of our work include tissue engineering and regenerative medicine. |
Monday, March 15, 2021 11:54AM - 12:06PM Live |
B11.00003: Cell cycle dependent mechanics drive epithelial stratification John Devany, Robert M Harmon, Margaret Gardel Epithelia have multiple spatial domains which perform specific tasks, e.g. crypts and villi in the intestine. This spatial organization can be disrupted in disease and is often associated with loss of tissue function. One of the key differences between these compartments is that some are highly proliferative, while others contain mainly non-proliferative cells. Cells drastically change their proliferation rates when they differentiate and move between these compartments, however, it remains unclear how these differences in proliferation affect epithelial organization. Here we focus on skin as a model system which can build these compartments starting from a single layer of stem cells. We heterogeneously express cell cycle inhibitors during the formation of skin organoids to measure how perturbing proliferation can change the organization of cells in the skin. We show that cells which become arrested in the cell cycle are more likely to exit the stem cell layer. By measuring contacts between cell-cell and cell-substrate interfaces we show that cell mechanics and adhesion are altered during the cell cycle. Together with theoretical modeling we show that these cell cycle dependent changes in cortical mechanics are an important driver of cell organization in the skin. |
Monday, March 15, 2021 12:06PM - 12:18PM Live |
B11.00004: Non-equilibrium Rigidity Transitions in Embryonic Tissues Sangwoo Kim, Marie Pochitaloff, Georgina Stooke-Vaughan, Otger Campas The physical state of embryonic tissues emerges from collective interactions among constituent cells. Here, we present a computational framework that includes key features at the cellular level, namely the presence of extracellular spaces, complex cell shapes and tension fluctuations that enables the description of non-equilibrium dynamics and emergent mechanics in embryonic tissues. We capture two limits of previously reported rigidity transitions in equilibrium (jamming transition and density-independent transition) and elucidate a novel non-equilibrium transition governed by junctional tension fluctuations. We find that tissues are maximally rigid at the structural transition between confluent and non-confluent states, with active tension fluctuations controlling stress relaxation and tissue fluidization. Comparing the simulation results to developing tissues during zebrafish body axis elongation, we show that tissues are solid-like and behave like wet foams at short timescales, with adhesion levels controlling the degree of cellular confinement. However, active T1 transitions by tension fluctuations control long timescale stress relaxation and tissue fluidization. Our results highlight an important role of non-equilibrium tension dynamics in developmental processes. |
Monday, March 15, 2021 12:18PM - 12:30PM Live |
B11.00005: Unified theoretical framework for epithelial mechanics, rheology and 3D shaping by upscaling active gels models of the actin cortex Adam Ouzeri, Sohan Kale, Alejandro Torres-Sánchez, Marino Arroyo Recent observations across various species have revealed a rich phenomenology of epithelial mechanics arising from the active-viscoelasticity and turnover of the actomyosin cortex. However, a link between the subcellular cortical dynamics and the tissue scale response has been lacking in theoretical models of epithelia. We address this gap by developing a formalism which bridges the active-gel models of the cortex and vertex-like models at a tissue scale. We show that this modeling approach provides a unified framework capturing numerous seemingly disconnected epithelial phenomenologies such as stress relaxation following step-strain maneuvers (Casares et al, Nat. Mat., 2015; Khalilgharibi et al, Nat. Phys., 2019), solid-like or fluid-like creep behavior (Harris et al, PNAS, 2012), buckling and transient buckling upon compression (Wyatt et al, Nat. Mat., 2020), pulsatile contractions during Drosophila dorsal closure (Solon et al, Cell, 2009), spontaneous curling (Fouchard et al, PNAS, 2020) and active superelasticity (Latorre et al, Nature, 2018). Overall, the proposed framework provides a systematic procedure to examine the effect at the epithelial scale of sub-cellular cortical dynamics and, in the process, ties a diverse epithelial phenomenology to a common subcellular origin. |
Monday, March 15, 2021 12:30PM - 12:42PM Live |
B11.00006: Collective pack size during cell migration modulated by an apparent cell-substrate friction Kelly Vazquez, Jacob Notbohm Collective cell migration is a dynamic biophysical phenomenon that is critical for wound healing, tumor invasion, and development. Cells are active and as such they produce cell-substrate and cell-cell forces which balance to bring about motion. During collective migration, cells form cohesive groups such as finger-like protrusions and coordinated packs; however, the underlying physical mechanisms controlling the size of these packs remain unclear. In most theoretical models, the connection between force and motion is governed by an apparent viscous friction at the cell-substrate interface. Here we conduct experiments to test two physics-based theoretical models that relate cell-substrate friction to either the size of a collective pack within the monolayer or the size of a protrusion at the leading edge. Increasing both time in culture and substrate stiffness affected the pack size within the monolayer and the protrusion size at the leading edge in a manner consistent with increased cell-substrate friction in the theoretical models. Thus, our experimental observations suggest that the size of collective cell packs and of protrusions at the edge of a cell layer depend on the magnitude of cell-substrate friction. |
Monday, March 15, 2021 12:42PM - 12:54PM Live |
B11.00007: Predictive understanding of discrete cell-fate decision in early embryonic development Jiaxi Zhao, Mindy Liu Perkins, Matthew Norstad, Jacques Bothma, Hernan G. Garcia One of the most remarkable features of life is a single cell's ability to make precise decisions in response to internal and external cues. These decisions are controlled by interconnected gene regulatory networks encoded by the information contained in the genomic DNA. Biology has made tremendous advances in identifying the regulatory networks that contribute to cell-fate decisions, but these studies often lack predictive theory. Positive autoregulation has been proposed as a general mechanism for establishing and maintaining these discrete cell-fate decisions. Here, we quantitatively dissect the role of autoregulation and bistability in establishing binary cellular fates in the fruit fly Drosophila melanogaster. Specifically, we apply recently developed single-cell live imaging techniques to quantify transcriptional and protein dynamics of the Drosophila pair-rule gene fushi tarazu as cells decide whether to commit to the expression of the gene. |
Monday, March 15, 2021 12:54PM - 1:30PM Live |
B11.00008: Engineering biological machines from living tissues Invited Speaker: Mahmut Selman Sakar Engineered tissues have the potential to serve as sensing, actuation, and mechanical support elements for soft machines that possess biomimetic functionality. Conventional biohybrid constructs involve the use of synthetic structures made from hydrogels or elastomers as support elements because free-standing contractile tissues do not have a stable form. In this talk, I am going to explain how physical principles of morphogenesis can be harnessed for the controlled self-assembly of tissues with complex equilibrium shapes. The discovery of these principles involves the use of advanced microscopy, robotic microsurgery, microtechnology, and computational modelling. Combined with our efforts in the development of genetically engineered skeletal muscle biological actuators, we can finally envision the conception of reconfigurable and self-healing robots that are autonomously assembled from living matter. |
Monday, March 15, 2021 1:30PM - 1:42PM Live |
B11.00009: Multi-tissue mosaics of homotypic and heterotypic cell monolayers Matthew Heinrich, Avi Wolf, Daniel Cohen, Andrej Kosmrlj We developed a framework for predicting the interaction of multiple expanding cell monolayers that fuse into one large monolayer. Individual epithelial monolayers expand at a constant outward speed and thus the evolution of their shapes can be predicted using the Huygens principle. To quantify tissue interactions, we investigated collisions of pairs of homotypic epithelial monolayers with different tissue shapes, densities, and sizes. Upon tissue collisions, their boundaries can move by a few cell lengths but they eventually “freeze” due to the contact inhibition of locomotion. For collisions of three tissues, we sometimes observe very narrow planar extrusions, when one of the tissues reaches high enough migration speed to stay ahead of the other two converging tissues. Based on these observations, we developed a computational model to predict the evolution of multi-tissue mosaics by using the Huygens principle of expanding tissues, whose boundaries freeze upon collisions. Without any fitting parameters, this model accurately predicts large scale morphology of multi-tissue mosaics of homotypic and heterotypic cell monolayers, where the mismatch of migration speeds for different cell types can lead to phenomena like total engulfment. |
Monday, March 15, 2021 1:42PM - 1:54PM Live |
B11.00010: Tissue pressure and cell traction compensate to drive robust aggregate spreading Muhammad Sulaiman Yousafzai, Vikrant Yadav, Sorosh Amiri, Michael F Staddon, Alan Tabatabai, Youssef Errami, Gwilherm Jaspard, Sirine Amiri, Shiladitya Banerjee, Michael Murrell In liquid droplets, the balance of interfacial energies and substrate elasticity determines the shape of the droplet and the dynamics of wetting. In living cells, interfacial energies are not constant, but adapt to the mechanics of their environment. As a result, the forces driving the dynamics of wetting for cells and tissues are unclear and may be context specific. In this work, using a combination of experimental measurements and modeling, we show the surface tension of cell aggregates, as models of active liquid droplets, depends upon the size of the aggregate and the magnitude of applied load, which alters the wetting dynamics. Upon wetting rigid substrates, traction stresses are elevated at the boundary, and tension drives forward motion. By contrast, upon wetting compliant substrates, traction forces are attenuated, yet wetting occurs at a comparable rate. In this case, capillary forces at the contact line are elevated and aggregate surface tension contributes to strong outward, pressure-driven cellular flows. Thus, cell aggregates adapt to the mechanics of their environments, using pressure and traction as compensatory mechanisms to drive robust wetting. |
Monday, March 15, 2021 1:54PM - 2:06PM Live |
B11.00011: Regulation of Three-Dimensional Epithelial Cell Shape in a Two-Dimensional Tissue Theresa Chmiel, Margaret Gardel Three-dimensional force distribution within the actin cytoskeleton of epithelial tissue regulates cell shape. While two-dimensional cell shape has been well characterized and heavily studied, three-dimensional cell shape regulation is less well understood despite its critical role in large scale epithelial processes such as invagination. By examining the relationship between cell height, density and biological components of the actin cytoskeleton, we explore the mechanisms by which the epithelial tissue regulates shape and volume. By probing the effect of external environmental forces on a tissue’s shape, we observe that while cell density is not a strong indicator of epithelial height, osmotic shock and substrate curvature drastically decreases both tissue height and cell volume while leaving the lateral shape of cells in the tissue undisturbed. In addition, we examine how the maturity of the tight junction regulates local volume and height correlation in the tissue. |
Monday, March 15, 2021 2:06PM - 2:18PM Live |
B11.00012: Controlled neighbor exchanges drive glassy behavior, intermittency and cell streaming in epithelial tissues Amit Das, Srikanth Sastry, Dapeng Bi Cell neighbor exchanges are integral to tissue rearrangements in biology, including development and repair. Often these processes occur via topological T1 transitions analogous to those observed in foams, grains, and colloids. However, in contrast to non-living materials, the T1 transitions in biological tissues are rate-limited and cannot occur instantaneously due to the finite time required to remodel complex structures at cell-cell junctions. We study how this rate-limiting process affects the mechanics and collective behavior of cells by introducing this biological constraint in a vertex-based model as an intrinsic single-cell property. We report in the absence of this time constraint conventional motility-driven glass transition is observed characterized by a sharp increase in the intermittency of cell rearrangements. Remarkably, this glass transition disappears as T1 transitions are temporally limited. A unique consequence of limited rearrangements is also that the tissue develops spatially correlated streams of fast and slow cells, in which the fast cells organize into stream-like patterns with effective leader-follower interactions and optimally stable cell-cell contacts. We also compare the predictions with existing in-vivo experiments in Drosophila pupal development. |
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