Bulletin of the American Physical Society
APS March Meeting 2023
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session T06: Mechanics of Cells and Tissues IV |
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Sponsoring Units: DBIO Chair: Abdul Malmi Kakkada, Augusta University Room: Room 129 |
Thursday, March 9, 2023 11:30AM - 11:42AM |
T06.00001: Cell division and differential adhesion drive cell self-segregation during embryo morphogenesis. Xinzhi Li, Dapeng Bi
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Thursday, March 9, 2023 11:42AM - 11:54AM |
T06.00002: Mechanosensing directs invasion and morphodynamics of spheroids Austin Naylor, Christopher Z Eddy, Bo Sun Mechanosensing is one way that cells and tumors interact with their local environment. As tumors grow and invade into the surrounding extracellular matrix (ECM), they are constantly sensing the ECM to help determine their course of action. Most studies up to date have either been on the single-cell level, or have used organoids as the major tumor model for mechanosensing experiments. By using spheroids as the tumor model, we are able to create a more physiologically relevant model for how tumors react to various mechanical cues in the ECM. By changing both the density and crosslinking of type 1 collagen gels, we are able to create a spectrum of mechanical cues to measure the invasion profiles and morphodynamics of the spheroids. We find that both the invasion profiles and morphodynamics are highly dependent on the stiffness of the ECM. |
Thursday, March 9, 2023 11:54AM - 12:06PM |
T06.00003: Kinetics of cellular aggregation: growth, power laws, and distinct mechanisms of cell-cell interactions Rumi De, Debangana Mukhopadhyay One of the fundamental aspects of developmental biology is the ability of cells to aggregate and form tissues. Cell aggregation is a complex process orchestrated by various interactions depending on its environment. Different interactions give rise to different pathways of cellular rearrangement and the development of specialized tissues. In this theoretical work, we investigate the spontaneous emergence of tissue patterns from an ensemble of single cells on a substrate following three leading pathways of cell-cell interactions: direct cell adhesion contacts, matrix-mediated mechanical interaction, and chemical signaling. We find that the average domain size and the mass of the clusters exhibit a power law growth in time under certain interaction mechanisms. Further, as observed in experiments, the cluster size distribution can be characterized by stretched exponential functions showing distinct cellular organization processes. Our analysis shows that the growth kinetics of the aggregation process are distinctly different for each pathway and can uniquely mark the differences between different cell-cell communication pathways and identify specific cellular growth processes. |
Thursday, March 9, 2023 12:06PM - 12:18PM |
T06.00004: Instabilities in hexanematic models of epithelia Josep-Maria Armengol-Collado, Livio Nicola Carenza, Luca Giomi Epithelial tissues, whose study remain fundamental to understand processes such as cancer progression, have revealed to exhibit multiscale orientational order. While the large scale dynamics is ruled by the nematic symmetry, hexatic order instead controls the behavior of small clusters of cells. By considering a hydrodynamic approach, we investigate the stability of hexanematic liquid crystals identifying the role of activity and flow alignment in the generation of spontaneous flows, which also reflect the interplay between different length scales. We finally address possible consequences when confining such a fluid in a channel, connecting this phenomenology with recent observations of metastatic cell invasion. |
Thursday, March 9, 2023 12:18PM - 12:30PM |
T06.00005: Multiscale measurements of mechanical stress in 3D co-cultures using a deformable micro-device Charles N Baroud, Shreyansh Jain, Hiba Belkadi, Martin Genet A wide range of methods are available to measure cellular mechanics, with a view of differentiating cancerous vs. normal cells. However there is a lack of a high-throughgput methods to measure the mechanics of multi-cellular aggregates, even though these provide much better models of health and disease. In addition to single-vell mechanics, understanding the tissue levels mechanical properties must account for cell-cell contacts, extra-cellular matrix, geometric factors, etc. Here we present a method to actuate and observe many multicellular aggregates, such as spheroids or organoids, within a single deformable micro-device. Heterogeneous mechanical properties within each tissue can be quantified by analyzing the deformation field of the tissue under stress and comparing with Hertzian mechanics. The variations in local properties can be related to the cellular parameters by analyzing the actin organization and nuclear shapes at the single-cell level. Then using confocal microscopy it is possible to construct a 3D graph of the deformation field, under mechanical forcing, with a sub-cellular resolution. Cellular rearrangements and re-orientation can be observed, as well as local membrane elongation and nuclear deformation. These measurements allow us to link the global deformations with the mechano-biological response of individual cells and to contrast the response of cancerous vs. non-malignant cells to mechanical forcing. |
Thursday, March 9, 2023 12:30PM - 12:42PM |
T06.00006: Mechanoregulation of biofilm homeostasis Sourabh Monnappa Kuppanda Jafri, Selman Sakar, Alexandre Persat Microbial communities are commonly found as biofilms: contiguous groups of cells held together by a self-secreted extracellular matrix of polymeric substances. To maintain the cohesion of the biofilm or to enable dispersal, cells must regulate matrix production. During growth, single biofilm-dwelling cells generate a mechanical stress onto the viscoelastic matrix. These forces influence biofilm architecture and morphogenesis. However, how they regulate the physiology of the cell population in the biofilm is unknown. To explore the relationship between constrained growth and bacterial decision-making, we investigated the physiology of bacteria confined in synthetic hydrogel matrices. We embed P. aeruginosa, a model organism for biofilm studies and an opportunistic pathogen, in PEG-hydrogels. By tuning the mechanical properties of the hydrogel, we found that the size of embedded biofilms decreases with the stiffness of the surrounding hydrogel. We show that measurements of the transcriptional profiles of embedded cells allow us to identify potential mechanosensors regulating biofilm integrity. Finally, using reporter fusions to monitor the transcriptional response of single PEG-embedded cells, we demonstrate that cells respond to constrained growth. Altogether, our study will highlight the role of mechanics in guiding cellular decisions within a biofilm. |
Thursday, March 9, 2023 12:42PM - 12:54PM Author not Attending |
T06.00007: Theoretical and computational modelling of cell-cell adhesion Pradeep K Bal, Marino Arroyo Cell-cell adhesion and decohesion are important in biology, to keep cellular tissues together and, in addition, to allow the disengagement of cells during remodeling. Due to the fluid nature of the surface of animal cells, the molecular bonds that keep cells together are laterally mobile. These molecular bonds form clusters, attach to the cytoskeleton through mechanosensitive adapter protein molecules, and undergo turnover by endocytosis. Cells can tune various properties of these molecular bonds including diffusivity, stiffness, and force sensitivity. We lack a fundamental understanding of how mechanics, chemistry, and biological regulation integrate to support the adaptable function of cell-cell adhesion, and how effective mechanical properties of adhesions such as strength and toughness depend on the molecular properties of bonds. The main objective is to develop a mathematical and computational model for cell-cell adhesion in full 3D generality coupling the active gel model of the actomyosin cortex to the adhesion dynamics of cell adhesion molecules of the Cadherins family. It allows us to understand how the actin cortex and the adhesion complexes work together to give rise to adaptable junctions and how the self-organization of the adhesion complexes takes place. We show how the interplay of mechanics and chemistry at adhesion patches leads to a wide range of behaviors that cells can use to stabilize cell-cell junctions during physiological stretch or to selectively detach during morphogenesis. |
Thursday, March 9, 2023 12:54PM - 1:06PM |
T06.00008: Rigidity of 3D confluent tissue is governed by energy barriers to local reconnection events Shabeeb Ameen, J. M Schwarz, Tao Zhang Cellular-based models of tissue can undergo rigidity transitions. We investigate three-dimensional vertex model for confluent |
Thursday, March 9, 2023 1:06PM - 1:18PM |
T06.00009: Investigating the density variation of fibroblasts near topological defects Kirsten D Endresen, Kurmanbek Kaiyrbekov, Brian A Camley, Francesca Serra Fibroblasts in dense populations have long-range nematic order. They also display topological defects, disordered regions within the ordered fluid. We grow 3T6 fibroblasts in monolayers on poly-dimethyl-siloxane patterned with ridges with heights ranging from 1.5 to 14 microns. These ridges are designed to guide the cells into forming topological defects with azimuthal circular alignment and hyperbolic alignment at controlled locations, allowing us to study how they impact the behavior of the fibroblasts. Near circular defects the cells reach a higher density than the rest of the monolayer while near the hyperbolic defects the density remains low. We investigate the role of collective migration in this behavior by varying the height of the topographic features and studying their resulting distributions and dynamics. By increasing the height of ridges, we decrease the probability of cells crossing ridges, limiting their ability to migrate collectively. However, we find that even on substrates with 14um ridges, taller than the cells, the locally increased density near circular defects is not suppressed, but rather enhanced. This finding supports another proposed mechanism for this density variation, which is due to a difference in the cell proliferation near defects. |
Thursday, March 9, 2023 1:18PM - 1:30PM |
T06.00010: Emergent chirality in active solid rotation of pancreas spheres Tzer Han Tan, Aboutaleb Amiri, Irene Seijo-Barandiarán, Michael F Staddon, Anne Materne, Charlie Duclut, Sandra Tomas, Marko Popovic, Anne Grapin-Botton, Frank Jülicher Collective cell dynamics play a crucial role in many developmental and physiological contexts. While two-dimensional (2D) cell migration has been widely studied, how three-dimensional (3D) geometry and topology interplay with collective cell behavior to determine dynamics and functions remains an open question. In this work, we elucidate the biophysical mechanism underlying rotation in spherical tissues, a phenomenon widely reported both in vivo and in vitro. Using murine pancreas-derived organoids as a model system, we find that epithelial spheres exhibit persistent rotation, rotational axis drift and rotation arrest. Using a 3D vertex model, we demonstrate how the interplay between traction force and polarity alignment can account for these distinct rotational dynamics. Furthermore, our analysis shows that the spherical tissue rotates as an active solid and exhibits spontaneous chiral symmetry breaking. Using a continuum model, we demonstrate how the types and location of topological defects in the polarity field underlie this symmetry breaking process. Altogether, our work shows that tissue chirality can arise via topological defects in the pattern of cell traction forces, with potential implications for left-right symmetry breaking processes in morphogenetic events. |
Thursday, March 9, 2023 1:30PM - 1:42PM |
T06.00011: Dynamics of exciton polaron in microtubule NGANFO YIFOUE WILLY ANISET In this paper, we study the dynamical properties of the exciton-polaron in the microtubule. The study was carried out using a unitary transformation and an approximate diagonalization technique. Analytically, the modeling of exciton-polaron dynamics in microtubules is presented. From this modeling, the ground state energy, mobility, and entropy of the exciton-polaron are derived as a function of the parameters characterizing the microtubule geometry. Numerical results show that, depending on the three vibrational modes (protofilament, helix, antihelix) in MTs, exciton-polaron energy is anisotropic and is more present on the protofilament than the helix and absent on the antihelix. The quasiparticles move only on the protofilaments and helix and when we take into account the variation of the protofilament vibrations by fixing the helix vibrations, the quasi-particles move between the 1st and 2nd protofilaments. When we take into account the variation of the two vibrations the quasi-particles move between the 1st and 15th protofilament. This result confirms the importance of helix vibrations on the dynamics of quasiparticles. The exchange of information between the exciton-polaron and its environment is similar to its mobility. Confirming that the quasiparticles move in the protofilament faster than the helix, the electrical field produced by the vibrations of the MT lattice may be anisotropic depending on the modes of vibration. |
Thursday, March 9, 2023 1:42PM - 1:54PM |
T06.00012: Slicing softly with paper Sif Fink Arnbjerg-Nielsen, Matthew D Biviano, Kaare H Jensen Paper cuts are a minor nuisance, but they can lead to life-threatening microbial infections. The physical processes that determine whether paper cuts into the skin, however, remain poorly understood. To explore skin-paper interactions, we designed an experiment in which a piece of paper contacts an artificial finger made from ballistic gelatin. Our experiments suggest that the paper thickness is one of the most important parameters in determining cutting efficacy. A relatively thin sheet often buckles before cutting is initiated, whereas the predominant interaction with thick sheets is indentation. Our preliminary data indicate that a successful paper cut is physically impossible outside a relatively narrow range of thicknesses for a given angle. Finally, the optimal paper cut is explored, and the influence of skin properties and cutting angle is discussed. |
Thursday, March 9, 2023 1:54PM - 2:06PM |
T06.00013: Particle Based Simuation of the Assembly and Mechanical Remodeling of Vascular Network Suraj K Sahu, Ajay Gopinathan, Suzzane Sindi, Mikahl Banwarth-Kuhn, Jose Zamora Using particle based simulation, we model the formation of preliminary vascular networks from individual endothelial cells during embryogenic development. During this process, also known as vasculogenesis, endothelial cells along with a myriad of other primitive cells form the primary vascular networks in presence of growth factors. This then acts as the foundation for the latter stages of vascular development. We show that single cell level properties like cell adhesion, contact inhibition of locomotion and response to mechanical stresses can affect network topology and the distribution of stresses within the network. We show that these features play important roles in network remodeling and maturation. We then compare our results with experiments and find single cell properties that produce efficient and robust vascular networks. |
Thursday, March 9, 2023 2:06PM - 2:18PM |
T06.00014: Stiffness-driven Human Hepatocytes Dysfunction via Metabolic-Redox Cross Talk in Liver Fibrogenesis Srivatsan Kidambi Liver stiffness (LS) is currently the best clinical predictor of liver fibrosis. However, the molecular mechanisms that account for the stiffness predilection to hepatocytes dysfunction have been underexplored. The overall goal of this study is to introduce a new paradigm that LS is a driver of hepatic dysfunction during fibrosis. Using a multidisciplinary approach, we investigated the role of LS in altering redox-bioenergetic network driving hepatocytes dysfunction. Primary human hepatocytes (PHH) were cultured on an innovative biomimetic platform “BEASTS (Bio-Engineered Adhesive Siloxane substrate with Tunable Stiffness)” that recreates physiologic (2 kPa) and pathologic stiffness (8, 15, 25, 55 kPa). We demonstrated that stiffness impedes urea, albumin production, and expression of drug transporter gene and epithelial cell phenotype markers. NMR metabolomics demonstrated that stiffness regulates metabolic pathways in PHHs including glycolysis, glutamate metabolism, TCA cycle, GSH metabolism, and mitochondrial function. Also, PHHs on fibrotic stiffness inhibits ATP production and maximal respiration and increases glycolysis and glycolytic capacity which parallels metabolic changes observed in fibrosis patients. PHHs cultured on fibrotic stiffness increased ROS; and decreased reduced glutathione levels culminating in apoptosis. Similar metabolic changes were observed in hepatocytes isolated from TAA-induced liver fibrosis in vivo model. These data demonstrates the plausible role of LS in driving hepatocytes dysfunction via redox-metabolic crosstalk during fibrosis. |
Thursday, March 9, 2023 2:18PM - 2:30PM |
T06.00015: Cell shape and fate changes in 3D model of mammalian hair follicle development Elizabeth Lawson-Keister, Ali Hashmi, Clementine Villeneuve, Sara A Wickström, M Lisa L Manning During mammalian skin development, a subset of basal cells within the epithelial compartment will alter their fate to specify into hair follicle cells. This collection of cells will compartmentalize, elongate and invaginate into the connective tissue under the epithelial layer to form a structure termed the placode. We investigate two possible mechanisms that might trigger this transition using an extended 3D Vertex model with features specific to skin, including additional heterotypic tension at interfaces between cells of different types. The first mechanism involves placode cells executing cell-autonomous changes in cell mechanics, e.g. altering myosin activity near the cortex or expression/localization of cell-cell adhesion molecules. A second mechanism involves a ring of fibroblast cells around the placode generating contractile forces which trigger the cell fate changes. We find both mechanisms can trigger elongation and invagination, and by quantitatively comparing model predictions for the placode's geometric and dynamic behavior to experiments we isolate the dominant mechanism at different developmental stages. |
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