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 Y11: Mechanics of Cells and Tissues VIFocus Live
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Sponsoring Units: DBIO Chair: Sujit Datta, Princeton University; Thomas Angelini, University of Florida |
Friday, March 19, 2021 11:30AM - 12:06PM Live |
Y11.00001: Award for Outstanding Doctoral Thesis Research in Biological Physics (2019): studying cellular behavior in jammed microgel growth media Invited Speaker: Tapomoy Bhattacharjee While the motion and collective behavior of cells are well-studied on flat surfaces or in unconfined liquid media, in most natural settings, cells thrive in complex 3D environments. Bioprinting processes are capable of structuring cells in 3D and conventional bioprinting approaches address this challenge by embedding cells in bio-degradable polymer networks. However, heterogeneity in network structure and biodegradation often preclude quantitative studies of cell behavior in specified 3D architectures. Here, I will present a new approach to 3D bioprinting and 3D culture of cellular communities that utilizes jammed, granular polyelectrolyte microgels as a support medium. The self-healing nature of this medium allows the creation of highly precise cellular communities and tissue-like structures by direct injection of cells inside the 3D medium. This 3D medium is also filled with nutrient which enables long time culture of cells and tissue-like structures. Further, the transparent nature of this medium enables precise characterization of cellular behavior. I will describe two examples of my work using this platform to study the behavior of two different classes of cells in 3D. First, I will describe how we interrogate the growth, viability, and migration of mammalian cells—ranging from epithelial cells, cancer cells, and T cells—in the 3D pore space. Second, I will describe how we interrogate the migration of E. coli bacteria through the 3D pore space. Together, these studies highlight how the jammed microgel medium provides a powerful platform to design and interrogate complex cellular communities in 3D—with implications for tissue engineering, microtissue mechanics, studies of cellular interactions, and biophysical studies of active matter. |
Friday, March 19, 2021 12:06PM - 12:18PM Live |
Y11.00002: Tissue cell behavior in packed microgel media Vignesh Subramaniam, Thomas Angelini Investigating how tissue cells interact and assemble within controlled 3D environments may lead to an improved understanding of how structured cell assemblies emerge in vivo. However, the inherent limits of using solid scaffolding or liquid spheroid culture for this purpose restrict experimental freedom in studies of cell assembly. Here we investigate how mono-culture and co-culture populations of cells interact and assemble using a 3D culture medium made from packed microgels as a bridge between the extremes of solid scaffolds and liquid culture. In this presentation, I will present work investigating the shape-evolution of non-spherical mono-culture liver tissue models embedded in packed microgel culture media. Additionally, preliminary work investigating how endothelial cells interact with hepatocytes in more complex liver tissue models will be presented. |
Friday, March 19, 2021 12:18PM - 12:30PM Live |
Y11.00003: Compression stiffening of fibrous networks with stiff inclusions Jordan Shivers, Jingchen Feng, Anne S. G. van Oosten, Herbert Levine, Paul Janmey, Frederick MacKintosh Various biological tissues stiffen under applied compression. However, due to their structural complexity, the mechanism for this stiffening is not obvious. Recent work has shown similar behavior in a simple tissue analogue consisting of a reconstituted biopolymer network containing inert colloidal particles. We show that compressing such a material can, under the right conditions, lead to significant rearrangement of the particles, which then heterogeneously deform the interstitial network. This leads to an unusual regime in which the mechanical response of the compressed material is controlled by the resistance of the interstitial network to stretching. Utilizing a coarse-grained model, we generate predictive phase diagrams for compression-driven stiffening and particle jamming as a function of particle volume fraction, network critical strain, and applied compression, which we test by simulating the rheology of disordered fiber networks containing rigid particles. |
Friday, March 19, 2021 12:30PM - 12:42PM Live |
Y11.00004: Fluid versus solid behaviour in a rheological constitutive model of tissue mechanics James Cochran, Junxiang Huang, Dapeng Bi, M Cristina Marchetti, Suzanne Fielding The deformation and flow properties of biological tissue are key to many important biological phenomena - including morphogenesis, wound healing and tumour metastasis - but remain poorly understood. In this work, we construct a continuum constitutive model of biological tissue rheology, aimed at describing the mechanics of a monolayer of confluent cells. The basic dynamical variables of the model comprise the cellular anisotropy and the degree of nematic alignment of elongated cells. We explore the model's rheological predictions, which include a yield stress in the solid phase. These predictions are compared with results from a mesoscopic vertex model of sheared biological tissue. |
Friday, March 19, 2021 12:42PM - 12:54PM Live |
Y11.00005: Intracellular Wave Dynamics Perturbed by Electric Fields and Nano-topography Qixin Yang, Matt Hourwitz, Leonard J Campanello, Peter Devreotes, John Fourkas, Wolfgang Losert Cells can respond to dc Electric Fields (EFs) by directed migration along the fields. This phenomenon, called electrotaxis, is an important physiological process involved in wound healing and regeneration. However, the mechanism of how cells sense EFs and coordinate intracellular activities remain elusive. Recent studies have observed self-organized waves of coupled signal transduction and cytoskeletal activities in various cell types, and both experiments and simulation show that these intracellular waves drive protrusions and regulate cell random migration. In this study, we explore the roles of these intracellular waves during electrotaxis, by monitoring the dynamics of actin waves in response to EFs. We use electrofused giant Dictyostelium discoideum cells, which provide a large spatial extent for wave dynamics in a single cell. Our quantifications show that EFs bias the preferred location of wave initiation, increase wave areas, and guide wave propagation towards cathodes. We further add nano-topographies to provide spatially inhomogeneous perturbation on wave dynamics and show that the waves generated from different local topographic environments respond to EFs differently. |
Friday, March 19, 2021 12:54PM - 1:06PM Live |
Y11.00006: Collective Motility and Mechanical Waves in Cell Clusters: A Molecular Clutch Model Youyuan Deng, Herbert Levine When epithelial cell clusters move collectively on a substrate, mechanical signals play a major role in the coherent behavior. There are a number of experimental results from traction force microscopy for a system of this type (MDCK cell clusters). These include: the internal strains are tensile even for clusters that expand by proliferation; the tractions on the substrate are confined to the edges of the cluster; in many cases there are waves; there is collective durotaxis of the cluster even though individual cells show no effect; and for cells in an annulus there is a transition between expanding clusters with proliferation and non-proliferating cases where cells rotate around the annulus. We formulate a simplified mechanical model which explains these effects in a straight-forward manner. The central feature of the model is to use a molecular clutch picture which allows “stalling” – inhibition of cell contraction and motility by external forces. Stalled cells are passive elements from a physical point of view and the un-stalled cells are active. When we attach cells to the substrate and to each other, and take into account contact inhibition of locomotion, we get a simple picture that gives the mechanical results noted above. |
Friday, March 19, 2021 1:06PM - 1:18PM Live |
Y11.00007: Mapping single cell mechanics as a function of environment geometry using Brillouin microscopy and optical tweezers microrheology Milos Nikolic, Giuliano Scarcelli, Kandice Tanner Cancer cells encounter a range of mechanical challenges as they invade secondary organs. Mechanical phenotype of the cell is a critical parameter that determines successful invasion and survival following deformations due to confinement, and physical forces. Here, we quantify the diversity of the mechanical states of live cells in biomimetic systems that recapitulate in vivo 2D and 3D environments. To measure cell mechanics on a sub-micrometer scale we use Brillouin microscopy (~GHz) and broadband frequency optical tweezer microrheology (3Hz-15kHz). We assessed the mechanical phenotype of U87 cell line in 2D and 3D environments where we tuned the substrate stiffness, dimensionality (3D versus 2D), and presence of fibrillar topography in 3D. We confirmed that the cells have higher Brillouin shift on rigid substrates, which is indicative of increased intracellular stiffness. Interestingly, cells embedded inside 3D hydrogels showed similar mechanical properties as the cells cultured on top of thick 2D hydrogels. We observed this using both Brillouin microscopy, and optical tweezers (G’=39±11Pa, G’’=25±7Pa at 19Hz). These findings are exciting as they confirm a correlation between two different measurement techniques that probe mechanics of live cells at different timescales. |
Friday, March 19, 2021 1:18PM - 1:30PM Live |
Y11.00008: Improved Chemotaxis by Repeated Stimulation Aravind Rao Karanam Chemotaxis, the chemically directed cell motion, is exhibited by several cell types in various contexts. Here, we study chemotaxis in the social amoeba Dictyostelium discoideum, which secretes and relays cyclic adenosine monophosphate (cAMP) during starvation. The resulting waves of cAMP that travel through the cell population result in aggregation and, eventually, lead to spore formation. |
Friday, March 19, 2021 1:30PM - 1:42PM Live |
Y11.00009: Bending instability of rod-shaped bacteria Luyi Qiu, Ariel Amir, John Hutchinson As can be intuited from everyday experience, a thin-walled tube (e.g., a drinking straw) subject to bending reaches a critical curvature at which an instability occurs, localizing the deformation into a narrow region. This instability has been extensively studied since the seminal work of Brazier nearly a century ago. However, the scenario of pressurized tubes has received much less attention. Motivated by rod-shaped bacteria such as E. coli, whose cell walls are much thinner than their radii and are subject to a substantial internal pressure, we study, theoretically, how such instability is affected by this internal pressure. We find that while the bending rigidity of the cell wall has almost no effect on the critical curvature, the internal (turgor) pressure significantly postpones the onset of the instability. |
Friday, March 19, 2021 1:42PM - 1:54PM Live |
Y11.00010: Multi-fractal analysis of the ossification process in developing skull bone Mohammadreza Bahadorian, Carl D Modes Different bones in vertebrates have different structural and functional roles. Long bones, such as the femur, exist under near continuous load and their development and formation reflect this role. Skullbone, on the other hand, exists in the entirely different context of occasional impact absorption in the service of protecting the brain. In spite of the importance of this function, the development of this tissue is not well-studied, mostly due to the complexity of the pattern by which the bone grows. We employ 2D multi-fractal analyses to study the ossification pattern of skull bone in developing mouse embryos. We first use the Multi-Fractal Detrended Fluctuation Analysis (MF-DFA) to investigate the multi-fractal features of the ossification patterns and their evolution over time. We then use multiple surrogates to determine the origin of the observed multi-fractality. Moreover, using the wavelet transform modulus maxima method, we obtain spatial information about the singularities whose spectrum is given by MF-DFA. We finally simulate some basic processes contributing to ossification and compare their analysis results to the ones from real data to rule out the processes which do not result in multi-fractality. |
Friday, March 19, 2021 1:54PM - 2:06PM Live |
Y11.00011: Talin manipulation in cell adhesion through an improved clutch model chiara venturini, Pere Roca-Cusachs, Pablo Saez Cell adhesion is a key mechanism in biological processes such as cell migration. The clutch model couples the contractile actomyosin cortex inside the cell with the extra-cellular matrix, through a number of adaptor proteins. It has been used to explain how cells can sense force and respond to substrate rigidity. Previous clutch models have provided fundamental understanding in cell adhesion. However, the adhesion composition has been oversimplified, limiting our understanding of how these multiple components of the adhesion influence cell adhesion mechanics. Here, we extend the classical clutch model with a detailed description of talin. Talin consists of a rigid head, a flexible neck and a rod made of 13 domains, which unfold and refold under force. Given the importance of the recruitment of adaptor proteins in a focal adhesion, we implement the presence of 11 vinculin binding sites (VBS) and 3 actin binding sites (ABS) in the talin rod. Our computational framework can easily manipulate VBS and ABS and analyze the effect of its depletion in the cell adhesion mechanics. We compare results of full talin rods and different combinations of talin domains depletion. We show dramatic changes in the traction forces and retrograde flow in our in-silico manipulations of the talin rod. |
Friday, March 19, 2021 2:06PM - 2:18PM Live |
Y11.00012: Topological braiding and bosonic phases on the cell membrane Jinghui Liu, Jan Totz, Pearson W Miller, Alasdair Hastewell, Jorn Dunkel, Nikta Fakhri Braiding of topological structures in complex matter fields provides a robust framework for encoding and processing information, and has been extensively studied in the context of topological quantum computation. By contrast, braiding of topological defects in the signaling waves of living systems remains poorly understood. Here, we investigate the self-organized Rho-GTP protein waves formed on the membrane of starfish egg cells during cell division. We show that the worldlines of spiral wave cores embedded in the signaling waves undergo rich spontaneous braiding dynamics, and are also capable of forming intricate loop structures. The worldline creation and annihilation events, topological entropy and braiding exponents, as well as loop statistics correlate with cellular activity and exhibit universal scaling behaviors, in agreement with predictions from a generic complex Ginzburg-Landau continuum theory with a tunable activity parameter. Our analysis further reveals that the braiding dynamics is dominated by same-sign defect pairs displaying bosonic exchange symmetry, suggesting an unexpected parallel between information processing processes in quantum and living matter, which can be further investigated using optical controls in this biological system. |
Friday, March 19, 2021 2:18PM - 2:30PM Live |
Y11.00013: An analytical model describing the E. coli cell wall as a pressurized elastic cylinder Octavio Albarran, Renata Garces, Christoph F. Schmidt Bacteria have tough shells that allow them to withstand large turgor pressures. In gram-negative bacteria, such as E. coli, shell toughness stems from the ~4 nm thick peptidoglycan layer cushioned between inner and outer lipid membranes. Under physiological conditions, the mechanical situation is analogous to that of a thin-walled pressurized elastic balloon. We here introduce a simplified analytical model to rationalize our experiments that compress E. coli between parallel plates while monitoring shapes, forces and indentation depths. In general –given the molecular structure of the peptidoglycan layer– the elastic response is expected to be non-linear and anisotropic. We provide evidence that deformations due to simple osmotic swelling permit a quantitative reading of the anisotropy. Comparison to experimental data shows consistency and allowed us to fix further parameters of the model. |
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