Bulletin of the American Physical Society
APS March Meeting 2018
Volume 63, Number 1
Monday–Friday, March 5–9, 2018; Los Angeles, California
Session A51: Physical Force Regulation of Cells and Tissue - IFocus Prize/Award
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Sponsoring Units: DBIO GSOFT Chair: MingMing Wu, Cornell Univ Room: LACC 511C |
Monday, March 5, 2018 8:00AM - 8:36AM |
A51.00001: Reciprocal coupling between cells and their mechanical environment Invited Speaker: Herbert Levine Contractile cells such as fibroblasts exert physical forces on the surrounding extracellular matrix ECM and these forces can lead to material remodeling. Conversely the structure of the ECM can determine the form of cell motility and cell-cell interactions. Here we describe the use of a simple lattice-based model coupled to experiments of cells in reconstituted collagen-based gels to study how contraction leads to both elastic and plastic deformations. We then argue that these deformations allow cells to affect each other with novel long-range (in time) interactions and that these may be responsible for patterns observed both in vitro and in tumor samples. |
Monday, March 5, 2018 8:36AM - 8:48AM |
A51.00002: Quantifying traction forces for different migration modes of Dictyostelium discoideum cells Elisabeth Ghabache, Jiangli Li, Marc Edwards, Peter Devreotes, Alex Groisman, Wouter-Jan Rappel Cell migration is omnipresent in a diverse set of biological processes, including wound healing, embryogenesis or cancer metastasis. During this migration, cells can use different modes of motility. For example, cells can exhibit amoeboid-like motion during which the morphology changes continuously. Alternatively, cells can move like fish keratocytes and maintain their shape for prolonged periods of time. Here, we study wild-type Dictyostelium discoideum cells, displaying amoeboid-like motion, and a mutant which exhibits keratocyte-like motion. We use Traction Force Microscopy, confocal microscopy and imaging of relevant cytoskeleton proteins to characterize these diverse modes of migration. In particular, we determine the distribution of forces for both the amoeboid-like and the keratocyte-like cells and quantify the correlation between these forces and the cell’s shape, size and speed. |
Monday, March 5, 2018 8:48AM - 9:00AM |
A51.00003: Quantifying the total mechanical tractions within aggregates of cells using microsphere traction force microscopy (MTFM) Aimal Khankhel, Bugra Kaytanli, Robert McMeeking, Megan Valentine Quantitative measurements of cell-generated mechanical forces have mostly been limited to two-dimensional substrates. While recent advances in three-dimensional measurements have provided useful insight, they have been limited to single-cell studies or only provide information on the local variations in these forces. Here we present the development of a force measurement method that uses cell-sized, compressible and elastic hydrogel microspheres (with diameters of 5-50 µm) as force sensors, thereby providing a solid cell-gel interface to promote natural cell-like interactions, and allowing measurements of nominal values of the cell-exerted forces, due to their inherent compressibility. In the analysis of the microsphere deformations, we use a boundary spectral method based on spherical harmonics decomposition of the traction field on the gel surface. Using the technique developed here, we quantify the total active traction profiles that aggregates of mammalian cells exert on the boundary of synthetic spherical hydrogel bodies and report the stress profiles within tumor-cell spheroids. |
Monday, March 5, 2018 9:00AM - 9:12AM |
A51.00004: Hyaluronan - a new player in adhesion and migration regulation Shlomi Cohen, Patrycja Kotowska, Patrick Chang, Rebecca Keate, Andres Garcia, Shuyi Nie, Jennifer Curtis Single and collective cell migration are fundamental in development, maintenance and the progression of diseases across multicellular organisms. Although the factors regulating adhesion and migration have been extensively studied, hyaluronan - a high molecular weight and microns long polysaccharide forming the pericellular matrix around migrating cells, has been mostly neglected. It is well established that an intermediate cell-substrate adhesion strength, given by an intermediate extracellular matrix density, produces maximum speed; while deviations from that density reduce it. Our data suggest that hyaluronan at the cell-substrate interface regulates the adhesion strength by exerting repulsive forces counteracting focal adhesions. While overexpression of hyaluronan has been shown to promote cell migration and the opposite for low expression levels, our preliminary data suggest a more complex relation. We show that the level of expression and the spatial distribution of hyaluronan at the cell-substrate interface, together with the surface density of extracellular matrix proteins, regulate cell adhesion and migration. |
Monday, March 5, 2018 9:12AM - 9:24AM |
A51.00005: Focal adhesion kinase is a reversible molecular mechanosensor Samuel Bell, Anna-Lena Redmann, Eugene Terentjev Sensors are the first element of signalling pathways that control the response of cells to their environment. Protein complexes that produce or enable a chemical signal in response to a mechanical stimulus are called ‘‘mechanosensors’’. Here we develop a theoretical model describing the physical mechanism of a reversible single-molecule sensor of mechanical stiffness of extracellular matrix, and apply it to focal adhesion kinase (FAK), which initiates the chemical signal in its active phosphorylated conformation, but can spontaneously return to its closed folded conformation. We find how the rates of conformation changes depend on the substrate stiffness and the pulling force applied from the cell cytoskeleton. We find the sensor is homeostatic, spontaneously self-adjusting to reach a state where its range of maximum sensitivity matches the substrate stiffness. We then consider several signalling pathways, via different Rho GTPases, leading to morphological changes in cytoskeleton, and to changes in cell motility, and compare with the detailed kinetics of experiments on cell spreading on different substrates. The results compare well with the phenotype observations of cells, allow to estimate the FAK activation energy, and suggest that the shortest pathway has 5 steps. |
Monday, March 5, 2018 9:24AM - 9:36AM |
A51.00006: To stick or not to stick - Chlamydomonas Microalgae Switch their Adhesiveness by Light Christian Kreis, Marine Le Blay, Christine Linne, Marcin Makowski, Oliver Baeumchen Optimization through adaptation to the natural habitat represents a general theme in the evolution of life that can be readily observed for cells, microorganisms and even higher-level animals. For microbial life, the ability to adhere to surfaces is ultimately linked to the formation of dense populations called biofilms, which may help to protect the community of cells against external stimuli. In contrast to marine phytoplankton, many photoactive microalgae live in complex environments, such as liquid-infused soil and moist rocks, where they encounter and colonize a plethora of surfaces. We discovered that the adhesion of green microalgae to surfaces can be reversibly switched on and off by light (C. Kreis et al., Nature Physics, 2017). Using a novel micropipette force spectroscopy technique, we measured in vivo single-cell adhesion forces and show that the microalga's flagella provide light-switchable adhesive contacts with the surface. This light-induced adhesion to surfaces is an active and completely reversible process that occurs on a timescale of seconds. Light-switchable adhesiveness is regulated by a blue-light photoreceptor and mediated by flagella membrane proteins that realise substrate-unspecific adhesive contacts. |
Monday, March 5, 2018 9:36AM - 9:48AM |
A51.00007: Synergy of Cells and Substrate in Cell Migration Abdel-Rahman Hassan, Thomas Biel, Taeyoon Kim Cell migration is a coordinated process that is ubiquitous in biology and plays a significant role in biological processes, such as morphogenesis, cancer metastasis, and tissue repair. To illuminate mechanisms of cell migration within a unified framework, we developed a versatile, computational model for cell migration on 2D substrates. The model incorporates lamellipodial dynamics as well as mechanical interaction between cells and substrate in a rigorous manner. We employed the model to recapitulate various aspects of individual and collective cell migration on deformable or stiff substrates. The model shows how persistent random walk is regulated at early and late stages. We show how durotaxis originates in mechanical interactions between cells and substrate; and how cells follow substrate alignment as contact guidance. We explain contact-inhibition of locomotion in a new way, and show how the collective migration behavior varies with cell density. Finally, we simulate how mechanical properties of deformable substrates dictate the evolution and patterning of cell ensembles. The predictive ability of this model can provide critical insights into diverse physiological and pathological phenomena. |
Monday, March 5, 2018 9:48AM - 10:00AM |
A51.00008: Cell Proliferation on Curved and Compliant Surfaces Ya-Wen Chang, Michael Tennenbaum, Michelle Gaines, Alexandros Fragkopoulos, Ricardo Cruz, Andres Garcia, Alberto Fernandez-Nieves Understanding aberrant epithelial collective cell growth is vital to addressing diseases such as cancer and organ fibrosis. The conditions of the extracellular microenvironment, including interfacial properties of the substratum (the surface in contact with epithelial cells) have a significant influence on the epithelial cell migration and proliferation. This work focuses on understanding the impact the substratum curvature has on cell behavior. We monitor the proliferation of MDCK epithelial cells on both planar and curved hydrogel substrates. The hydrogels used are made of polyacrylamide, and the curved surfaces have toroidal shape, with tube radius on the order of 200 um and an aspect ratio range between 1 to 10. Proliferation is quantified by identifying cells synthesizing DNA at fixed time points. The extend of proliferation and patterns they create on curved and planar substrates are compared. |
Monday, March 5, 2018 10:00AM - 10:12AM |
A51.00009: Effects of geometry and structural constraints on the mechanics of 3D engineered microtissues Prasenjit Bose, Jeroen Eyckmans, Christopher Chen, Thao Nguyen, Daniel Reich The structure of the extracellular matrix (ECM) in living tissues plays a critical role in facilitating numerous cellular functions. Hence, understanding and controlling the ECM structure is crucial for modeling various mechanobiological and wound healing processes. We have developed a platform to control ECM alignment in engineered microtissues, while simultaneously measuring their mechanical properties. Tissues are self-assembled from cell-laden collagen gels in microfabricated wells with protruding elastic pillars. The pillars control tissue shape and measure contractile forces. Magnetic material attached to one pillar per well allows application of tensile strain via a magnetic tweezer. Optical tracking of the pillars’ positions and the tissue’s local deformations provides readouts of force generation and the displacement field. Fibroblast populated microtissues grown on elongated isosceles triangular pillar geometries show aligned ECM and increased stiffness compared to microtissues with isotropically organized ECM grown on octagonal pillar structures. Finite element linear elastic modeling of the force and displacement data at low strains provides quantitative measures of the effective elastic moduli, and their spatial variation across the different microtissue geometries. |
Monday, March 5, 2018 10:12AM - 10:24AM |
A51.00010: Compressional stiffening of cells and the role of the cell nucleus Mahesh Chandrasekhar Gandikota, Katarzyna Pogoda, Tyler Engstrom, Paul Janmey, Jennifer Schwarz What happens to a stationary cell when it is squeezed to large strains? Does the cell become increasingly rigid with compressive strain (compression stiffening) - like a soft tissue? Or does it compression soften - like an isolated fibrous network? Since the cellular cytoskeleton that gives the cell its structural support, is composed of semiflexible polymers that can buckle, one might conclude that the cell softens as it is squeezed. Experiments, however, demonstrate that cells from the ear of a mouse exhibit Hookean behavior with a crossover to superlinear behavior (compression stiffening) at large strains. We present modeling demonstrating compression stiffening in cells using rigidity transitions as a framework and show how the mechanical coupling between the cytoskeleton and the nucleus affects the stiffening. Quantitative comparisons with the experiments will be made to demonstrate the validity of the modeling and to ultimately make predictions for experiments with other cell types. |
Monday, March 5, 2018 10:24AM - 11:00AM |
A51.00011: Mechanics and Variability of a Volvox Embryo Turning Itself Inside Out Invited Speaker: Pierre Haas Dissertation Award Winner |
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