Bulletin of the American Physical Society
APS March Meeting 2018
Volume 63, Number 1
Monday–Friday, March 5–9, 2018; Los Angeles, California
Session B51: Physical Force Regulation of Cells and Tissue - IIFocus
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Sponsoring Units: DBIO GSOFT Chair: MingMing Wu, Cornell Univ Room: LACC 511C |
Monday, March 5, 2018 11:15AM - 11:51AM |
B51.00001: Tumor cell invasion and metastasis in vivo Invited Speaker: Jeffrey Segall For a number of solid tumors, although the primary tumor may be removed by surgery, patients succumb to the disease due to spread of the tumor before surgery to other tissues, termed metastasis. We have studied the process of metastasis of breast cancer using in vitro and mouse models. Metastasis involves the local invasion of tumor cells into surrounding tissue, entry into blood vessels, travel through the bloodstream to distant sites such as the lung, arrest in the vasculature of the lung, extravasation into the lung, and growth. As a lung metastasis gets larger, it in turn can repeat this cycle, resulting in the spread of metastases throughout the body and eventual death of the patient. We have found that tumor associated macrophages can enhance a number of the steps of metastasis through paracrine interactions with tumor cells. In particular we have found and EGFR/CSF1R paracrine interaction to be important, in which CSF1 produced by tumor cells can stimulate nearby macrophages to in turn secrete EGF receptor ligands that can stimulate the tumor cells. This paracrine interaction can enhance local invasion and intravasation, resulting in increased metastatic capability. |
Monday, March 5, 2018 11:51AM - 12:03PM |
B51.00002: Cooperativity of cell crawling and active contractility regulates gap closure efficiency in tissues Michael Staddon, Dapeng Bi, Michael Murrell, Shiladitya Banerjee Many developmental processes, such as morphogenesis, wound repair, and apoptosis, involve the closure of tissue gaps to maintain mechanical integrity. Depending on the environment, gap closure is mediated by lamellipodial cell crawling, or by purse-string based contraction of a multicellular actomyosin cable. To investigate how these processes collectively regulate the rate of wound repair, we introduce a cell-based computational model for a wounded monolayer adherent to a soft substrate. By systematically varying substrate stiffness, wound geometry, and intercellular cohesion, we show that a mixture of purse-string and crawling is always efficient for faster gap closure, irrespective of cell and substrate properties. We find that substrate rigidity and tissue fluidity enhances the rate of wound repair, suggesting that the assembly of purse-string and lamellipodia are mechanosensitive. While crawling driven closure occurs at a constant speed, we find purse-string based closure is strongly sensitive to gap geometry. These results suggest that wounded tissues can modulate their cytoskeletal machineries in an adaptive manner to repair wounds efficiently in diverse environments. |
Monday, March 5, 2018 12:03PM - 12:15PM |
B51.00003: Ultra-Fast Contractions and Emergent Dynamics in a Living Active Matter - the Epithelium of the Primitive Animal Trichoplax adherence Shahaf Armon, Matthew Bull, Manu Prakash Non-muscle cellular contractions are a common way for animal cells/tissues to apply forces on their surroundings and/or shape themselves. In early evolution of multicellularity, epithelial contractions played a crucial role in keeping animal integrity and coordination, opposing and then replacing ciliary power. In most animals today epithelial contractions are associated with embryogenesis, where slow and precisely controlled contraction patterns are shaping the embryo. In this work we report the discovery of ultra-fast epithelial contractions (50% cell area in 1 second, an order of magnitude faster) in the early diverging, “simple" animal Trichoplax adherence, that lacks neurons or muscles. Using theoretical calculations, we demonstrate that the observed speeds can be explained by actin-myosin contractility with bundle geometry and minimal load. We show that the unique tissue architecture is indeed reducing the load on the molecular motors. Live imaging of the whole animal in vivo reveals emerging contraction patterns, including propagating waves. We hypothesize a new role of cellular contractions in epithelium - enabling resilience to rupture via "active cohesion". Studying this early epithelium highlights a novel unstudied realm in cell cytoskeleton as active soft matter |
Monday, March 5, 2018 12:15PM - 12:27PM |
B51.00004: The dynamics of multi-cellular coordination in a living fossil Matthew Bull, Shahaf Armon, Vivek Nagendra Prakash, Manu Prakash The tradeoff between stability of form and sensitivity to environment is central to the emergent dynamics of living systems. At the organism scale, one of the most successful strategies for addressing this challenge is the integration of a nervous system with complex signal processing capabilities. Informed by the perspective of a true living fossil, we study the physical constraints on multicellular collectives which existed before the nervous system. Through joint experimental study of the phylum placozoa – an early diverging sister group to all animals with no muscles or neurons – and agent based numerical work, we investigate the delicate interplay between sensitivity and stability in a parsimonious model (an active elastic sheet) calling upon concepts from active matter and embodied computation. We find that through local rules alone multicellular collectives can generate long-wavelength stability without compromising organism-wide sensitivity to local inputs. We describe a low-dimensional representation of organism scale dynamics in the form of a simple quasi-particle description. Finally, we demonstrate these the utility of these results in the context of behaviorally relevant settings including: local-global foraging, and tribotaxis (ascending frictional gradients). |
Monday, March 5, 2018 12:27PM - 12:39PM |
B51.00005: A coupled multi-scale mechanochemical computational model of growth regulation in the Drosophila wing disc Ali Nematbakhsh, Weitao Chen, Jamison Jangula, Jeremiah Zartman, Mark Alber How cells proliferate and know when to stop growing is an important question in development biology and medicine. Uncontrolled growth will lead to abnormal development or fatal disease including cancer. The Drosophila wing disc is a classical system used to study this question due to its simplicity and the richness of experimental data. However, the mechanism of growth regulation is still a subject of debate. Multiple hypotheses based on mechanical and/or chemical signaling have been proposed. However, they either lack experimental evidence or cannot account for all observations. We developed a subcellular mechanical model coupled with a 2D chemical signaling network model to test different hypotheses. The mechanical module provides positions and mechanical stress levels of cells to be used by chemical signaling module to direct the growth and division orientation of cells. Simulation results show that a hypothesized temporal Dpp signaling is not sufficient to describe the growth regulation. Low level of signals at the lateral side of the wing disc results in hyperproliferation and synchronized division of cells. We are currently testing role of coupled Wnt and Dpp signaling in achieving homogeneous growth. |
Monday, March 5, 2018 12:39PM - 12:51PM |
B51.00006: Epithelial Monolayers Display Different Modes of Traction Stress Organization Erik Schaumann, Michael Staddon, Guillermina Ramirez-San Juan, Shiladitya Banerjee, Margaret Gardel Monolayers of epithelial cells are characterized by both “classical” material properties as well as self-responsiveness and other properties defined by their non-equilibrium status, and as such pose interesting questions at the intersection of several disciplines. We have identified, in the case of wild type and zonula occludens (ZO) 1 and 2 dKD MDCK cells, at least two patterns of behavior in how monolayers distribute mechanical forces to their environment, i.e., traction stresses. In the first case, ZO dKD cells distribute stresses in analogy to an elastic contractile gel, results that agree with previous results from colonies of keratinocytes. The wild type cells, however, distribute stresses in contradiction to these results, notably in the movement of stress peaks over time. This underlines the need for a dynamic model of traction stresses; active matter provides natural candidates for such a model. A newly-developed active vertex model recapitulates the wild type behavior with a small set of tunable parameters. This, taken together with the experimental results, implies a spectrum of traction stress dynamics that could unify tissue-scale mechanics for several systems under one model. |
Monday, March 5, 2018 12:51PM - 1:03PM |
B51.00007: Unexpected Tissue Surface Tension in Simple Models of Dense Biological Tissues Daniel Sussman, Jennifer Schwarz, M Cristina Marchetti, M Manning Tissue surface tension, the effective interfacial tension between two tissues composed of different cell types, has been a useful paradigm for explaining cell sorting, compartmentalization, and boundary maintenance in vivo or in co-culture. Different experimental techniques have been developed to measure tissue surface tension by analogy with the equilibrium behavior of molecular fluids. An important open question is whether these different techniques probe the same thing, since tissues are far from equilibrium and cells have different degrees of freedom and interactions compared to molecules. We extend existing vertex-based models for confluent tissues by allowing individual cells to regulate the tensions between neighboring cells of like or unlike type, and then numerically measure the effective surface tension between coexisting cell populations. Strikingly, we find that different methods which yield identical values of the tension in molecular fluids differ by more than an order magnitude in confluent models for tissue. We demonstrate that this difference stems from the topological nature of the interactions between cells, and speculate that similar interfacial sharpening may occur in other systems with topological interactions. |
Monday, March 5, 2018 1:03PM - 1:15PM |
B51.00008: Decoding cell shapes, mechanical stress and collective dynamics in human bronchial epithelial cells. Amit Das, Jennifer Mitchel, Jin-Ah Park, Dapeng Bi It has been broadly recognized that the mechanical force transmission can be equally important as genetics and biochemistry in regulating tissue organization in various biological processes, including morphogenesis, wound healing and disease progression. In order to make useful predictions for large scale cell remodeling in tissues, we must understand their material properties, such as the forces that build up inside them, characterized by pressures and stresses and the spatial variation of these mechanical measures. Here we use the recently developed set of mechanical inference methods to investigate the inter-cellular stresses in cultured human bronchial epithelial cells. By assuming mechanical equilibrium, we infer the tensions along cell edges and pressures within each cell from the cell configurations. This method provides a spatial distribution of stresses and directly couples mechanics to morphology. We pay significant attention to any contribution from the 'rosette' configurations (cell vertices with connectivity of four or more) which are like the topological defects in a tissue. |
Monday, March 5, 2018 1:15PM - 1:27PM |
B51.00009: Mechanical and Biochemical Micromanipulation of Individual Suspended Cells Samaneh Rezvani Boroujeni, Nan Shi, Todd Squires, Christoph Schmidt Cells communicate with their environment through biochemical and mechanical interactions. They can respond to stimuli by undergoing shape- and, in some situations, volume changes. Key determinants of the mechanical response of a cell are the viscoelastic properties of the actomyosin cortex, effective surface tension, and osmotic pressure. It is challenging to measure the mechanical response of cells while changing environmental conditions. We here demonstrate the use of a novel microfluidic device with integrated hydrogel micro-windows to change solution conditions for cells suspended by optical traps. Solution conditions can be rapidly changed in this device without exposing the cells to direct fluid flow. We use biochemical inhibitors and varying osmotic conditions and investigate the time-dependent response of individual cells. Using a dual optical trap makes it possible to probe the viscoelasticity of suspended cells by active and passive microrheology and to quantify force fluctuations generated by the cells at the same time. |
Monday, March 5, 2018 1:27PM - 1:39PM |
B51.00010: Development of 3D stress field mapping for bioprinted cardiac tissue Seungman Park, Wei-Hung Jung, Chin Siang Ong, Matthew Pittman, Debonil Maity, Nicholas Yam, Narutoshi Hibino, Yun Chen Generating contractile forces, and withstanding compressive and stretching stress are requisite cardiac functions. With advancement in tissue engineering, it is critical to develop a systematic way to characterize mechanical behaviors in 3D engineered tissues to assure the quality of potential clinical applications. We mapped 3D stress fields in bioprinted cardiac tissues by dynamically tracking micron-sized particles labeling the tissue. Based on the displacement of the particles, values of three metrics were extracted: velocity, beating frequency, and contraction force using the modified Stokes’ Equation. The viscoelasticity of the tissue was assessed using magnetic tweezers. Combining the measurement results, force and stress were mapped to the tissue by finite element method (FEM). We observed that contractile frequency ranges from 0.5 Hz to 1 Hz, agreeing with the physiological heart rate. Force maps revealed that contractile forces are heterogeneous over the cardiac tissue. Computationally, 3D force/stress maps by FEM were modeled constitutively and compared with the measurement data. We conclude our new methods are accurate in informing functional properties of engineered cardiac tissues, and potentially applicable to clinical practice. |
Monday, March 5, 2018 1:39PM - 1:51PM |
B51.00011: Modeling Cell Motility Dependence on Substrate Adhesion Using the Phase-field Method Yuansheng Cao, Brian Camley, Herbert Levine, Wouter-Jan Rappel Migration of eukaryotic cell plays an important role in many biological processes including development, chemotaxis, and cancer metastasis. Despite significant experimental and theoretical efforts, the role of cell-substrate adhesions in migration is still unclear. Here, we use the phase-field approach to model adhesive interactions between cell and substrate and determine the relationship between adhesion and cell velocity. For this, we model a 2D cross-sectional slice with conserved area and with active stresses confined near the substrate. We find that as the adhesion strength increases, the cell spreads more, becomes thinner, and, surprisingly, moves faster. To further understand this, we study an analytical model for cell motility and find its results to be consistent with our simulations: cells with conserved volume experience a stronger adhesion and therefore spread more, reduce their height, and increase their speed. Furthermore, we extend the model by introducing an adhesion-dependent friction force and find that the velocity-adhesion curve is bell-shaped with a clear maximum. Our model provides an explanation for the experimentally observed biphasic dependence of cell motility on adhesion. |
Monday, March 5, 2018 1:51PM - 2:03PM |
B51.00012: Morphology and Motility of Cells on Soft Substrates Andriy Goychuk, David Brückner, Andrew Holle, Joachim Spatz, Chase Broedersz, Erwin Frey Cells are greatly influenced by the mechanical properties of their environment. To study the cellular response to traction-induced substrate deformations, we extend a cellular Potts model of actively polarizing cells with a coarse description of the viscoelastic substrate. Apart from the influence of substrate stiffness, we demonstrate the importance of dissipative effects in the form of viscous friction. |
Monday, March 5, 2018 2:03PM - 2:15PM |
B51.00013: Information Processing and Ca2+ Signals Around Epithelial Wounds Shane Hutson, Aaron Stevens, James O'Connor, Erica Shannon, Andrea Page-McCaw For epithelial cells to heal a wound, those cells must first detect the presence of a nearby wound. The earliest signal indicating such a detection is a cytoplasmic influx of Ca2+ ions. For laser-wounds in Drosophila epithelia, this Ca2+ influx is driven by both mechanical and biochemical signals: cellular micro-tears generated by cavitation-induced shear stresses and ligands released from lysed cells that activate their cognate receptors. Such Ca2+ signaling is dynamic, expanding outward from the wound in two stages over the course of seconds to minutes and then devolving into multi-cellular Ca2+ flares that continue for hours. We will discuss the information content of these dynamic Ca2+ signals and correlate the signals seen by individual cells with the degree to which those cells migrate, change shape and proliferate to help heal the wound. |
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