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 K10: Mechanics of Cells and Tissues III |
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Sponsoring Units: DBIO Chair: Kinjal Dasbiswas, University of California, Merced Room: Room 202 |
Tuesday, March 7, 2023 3:00PM - 3:12PM |
K10.00001: Cell size regulation and growth control in crowded tissues Logan C Carpenter, Shiladitya Banerjee Regulation of cell size and growth within a crowded tissue is critical to reach and maintain homeostasis. While most studies to date have characterized tissue homeostasis and growth control at the population-level, there are no available models that connect cellular growth dynamics and mechanics to the emergent tissue-level dynamics. Using parameters determined from experiments on cultured epithelial cells, we develop a multi-scale Cellular Potts model that describes the dynamics of a tissue transitioning from a sub-confluent state to a state of arrested growth. The model addresses how tissue crowding influences cell growth, size regulation and division dynamics. Using this model, we quantify how a cell's sensitivity to crowding, deformation, cell-cell adhesion, and susceptibility to apoptosis influence the dynamics of cell size and growth in multicellular environments. |
Tuesday, March 7, 2023 3:12PM - 3:24PM |
K10.00002: Adding learning degrees of freedom in biological tissues Sadjad Arzash, Indrajit Tah, Andrea J Liu, M Lisa L Manning Simple vertex models capture successfully many aspects of mechanical behavior of biological tissues, such as rigidity transitions. These cell-based models contain parameters such as preferred cell perimeters that govern the mechanics and dynamics of the system. Here, we allow these parameters to vary as new learning degrees of freedom to explore the mechanical rigidity of tissues. These additional degrees of freedom—on top of the physical degrees of freedom, namely the vertex positions—alter the energy landscape. We find that the rigidity transition can be shifted by introducing the preferred cell perimeters as transient degrees of freedom. Adding perimeter or area stiffnesses or preferred cell areas as new degrees of freedom, on the other hand, does not change the rigidity transition of tissues. |
Tuesday, March 7, 2023 3:24PM - 3:36PM |
K10.00003: Cellular Cruise Control: Energy dissipation regulates collective migration in epithelia Isaac B Breinyn, Simon Martina-Perez, Daniel J Cohen, Ruth Baker Collective cellular migration is crucial for several key biological processes such as wound healing, morphogenesis, and metastasis. The mechanisms that regulate this dynamic migratory behavior are a complicated consortium of intracellular cytoskeletal mechanics and signaling pathways, intercellular cell-cell adhesion, and extracellular interactions with the environment. Here, we develop a data-driven agent-based model that predicts collective migratory behavior from past energy dissipation alone, considering cell-substrate friction and viscous cell-cell interactions. Using this model, we are able to accurately predict tissue traction forces from phase microscopy data, removing the need for more invasive and complicated experimental methods such as TFM. Additionally, we show that cells self-regulate their migratory behavior and that the past energy expenditure of a cell is an accurate predictor of its future behavior. Finally, we perform canonical electrotaxis (the guided migration of cells experiencing an electrical current) experiments to show that exogenous migratory cues shift cell self-regulation to different modes of migration. Our model accurately recapitulates the phenomenon wherein epithelia exhibit a migratory slowdown when undergoing prolonged stimulation and has applications in developing closed-loop control of epithelial migration. |
Tuesday, March 7, 2023 3:36PM - 3:48PM |
K10.00004: Investigating the Effects of Laser Induced Cavitation Bubbles and Fast Calcium Influx in Wound Healing Mia Grace Cantrell A major challenge in biology and medicine is understanding the mechanisms of epithelial wound healing, i.e., identifying how an epithelial tissue repairs a wound through coordinated and patterned changes in cellular behavior. A key question is how the patterns of cell behavior relate to the patterns of cellular damage around a wound. To investigate this relationship, we make laser wounds in the notal epithelium of Drosophila pupae. Laser ablation makes a controlled and reproducible pattern of cellular damage via both plasma generation at the focus and a rapidly expanding and collapsing cavitation bubble, which applies shear stress that damages the plasma membrane of surrounding cells. The subcellular location of this damage can be tracked using the patterns of rapid calcium influx on millisecond time scales. We can also use fluorescent cell surface markers to track rapid displacements across the field of cells. Combining the displacement fields and patterns of fast calcium influx, we can relate shear-stress to damage around the wound and on to the pattern of cell behaviors observed on longer time scales. |
Tuesday, March 7, 2023 3:48PM - 4:00PM |
K10.00005: A mathematical model for tissue growth in a tissue-engineering scaffold pore Haniyeh Fattahpour, Pejman Sanaei A tissue engineering scaffold is composed of pores lined with cells that allow nutrient-rich culture medium to pass through, thereby encouraging the proliferation of cells. Growth of the tissue is affected by a number of factors, including the flow rate and concentration of nutrients in the feed, the elasticity of the scaffold, and the properties of the cells. Many studies have examined these factors separately, but in this project, we aim to examine all of them together. In this work, we (i) develop a mathematical model that describes the dynamics and concentration of nutrients, scaffold elasticity, and cell proliferation; (ii) solve the model and simulate the cell proliferation process; (iii) develop a reverse algorithm that determines the initial scaffold pore configuration based on the desired geometry of the final tissue. |
Tuesday, March 7, 2023 4:00PM - 4:12PM |
K10.00006: Time-dependent impact of texture sensing and adhesion on guided epithelial cell migration Corey Herr, Matt Hourwitz, Abby L Bull, John T Fourkas, Wolfgang Losert Cell motion is governed by internal factors, such as the actin cytoskeleton and molecular signaling pathways, but can also be influenced by external factors, such as topography and chemical signaling. These factors are often mediated by the cell's interaction with the extracellular matrix through, for instance, the sensing of chemicals or rigidity. These factors all influence the direction and extent of cell migration and actin cytoskeleton dynamics. The actin cytoskeleton has been shown to be one of the primary sensors of topography, and in the case of ridges, this sensing can be linked with altered cell guidance. We have investigated the interplay among three processes: sensing of, adhesion to, and guidance by the microenvironment. To explore this interplay, we study the migration and actin dynamics of MCF10A cells on a nanoridge surface coated with varying levels of Collagen IV. With increased Collagen IV concentration, we find that cells are more adherent and that the actin dynamics responds to the nanotopography more strongly. However, we find that the enhanced actin behavior does not distinguish between the separate guidance phenotypes. Finally, we observe that collagen-coated surfaces cause cells to travel large distances of up to 100 microns in straight paths despite the bidirectional bias in actin polymerization. |
Tuesday, March 7, 2023 4:12PM - 4:24PM |
K10.00007: A biomechanical model for epithelial defense against cancer Sayantani Kayal, Praver Gupta, Shilpa P Pothapragada, Tamal Das, Dapeng Bi Epithelial systems tightly regulate their homeostatic mechanism through an interplay between cell growth, proliferation, and death. Non-proliferative cell competition is one such established process that preferentially eliminates one cell population over another to preserve the tissue homeostasis, widely observed in the process of epithelial defense against cancer (EDAC). In this work we study in detail the contribution of tissue mechanics towards regulating non-proliferative cell competition in vitro and in silico. Using force microscopy techniques in vitro, we demonstrate that compressive stress emerges as a unique mechanical signature for competitive elimination of HRasV12-transformed cells. Further, using a combination of biophysical techniques, we identify homeostatic pressure differential, cellular compressibility, and junctional instability as the potential candidate for the origin of compressive stress. We use cell-based physical models to uncover the relative sensitivity of these biomechanical factors towards promoting cell competition. These findings collectively establish mechanical imbalance between the competing cell populations as the cue for compaction and subsequent loser cell elimination. |
Tuesday, March 7, 2023 4:24PM - 4:36PM |
K10.00008: Dynamics of cytokinesis failure in individual tumorigenic cells Maryam Kohram, Celeste Nelson Normal progression through the cell division cycle is essential for a healthy organism. Disruptions in the cell cycle can lead to a range of abnormalities, including the formation of a genomically unstable tumor. Failure of cytokinesis, the final step of the cell cycle, can result in multinucleation, which alone is sufficient to promote tumorigenesis. Multinucleation has also been associated with a resistance to chemotherapeutic drugs and an increased probability of mutations. Here, we investigated the spatiotemporal dynamics with which a mother cell fails to undergo cytokinesis and gives rise to multinucleated progeny. We compared two well-established cell lines: MCF10A human mammary epithelial cells, and SCp2 mouse mammary epithelial cells. On a cell-by-cell basis, we compared the morphologies and behaviors of mother cells that successfully completed cytokinesis with those that became multinucleated. These comparisons revealed several different parameters that influence cytokinesis, including the stiffness of the extracellular matrix, the migratory behaviors of the cells, and the relative lengths of different stages of the cell cycle. These findings influence our conception of how genomic instabilities that drive cancer progression are initiated. |
Tuesday, March 7, 2023 4:36PM - 4:48PM |
K10.00009: Substrate-mediated mechanical interactions induce multicellular network formation Patrick Noerr, Farnaz Golnaraghi, Ajay Gopinathan, Kinjal Dasbiswas Cells sense their surroundings by exerting mechanical forces on their viscoelastic substrate. We show, through agent-based simulations of cells modeled as motile, contractile force dipoles on elastic substrates, that mechanical interactions result in cell networks. These resemble networks of endothelial cells, a precursor to blood vessel formation. The morphology of the simulated networks is quantified by several metrics, including the percolation transition and a fractal dimension. Model networks are found to have a fractal dimension comparable to leaf and animal venation, and significantly lower than the control case of randomly moving adhesive agents. This shows that cells directed by substrate mediated elastic interactions can more efficiently form space-spanning structures. Next, we investigate the dynamics of cell-cell interactions by considering timescales from substrate viscoelasticity and force dipole generation. Additionally, we simulate a finite elastic medium, to examine the possible feedback between cell network formation and macroscopic gel contraction. |
Tuesday, March 7, 2023 4:48PM - 5:00PM |
K10.00010: Tension remodeling controls topological transitions in confluent tissues Fernanda L Pérez Verdugo, Shiladitya Banerjee Tissue fluidity, mediated by the exchange of cellular neighbors, is critical for large-scale cellular rearrangements during tissue morphogenesis, repair, and collective cell migration. Cellular neighbor exchange events rely on the instability of four-fold vertices that are formed when intercellular junctions shrink to a single point during contraction, followed by the junctions resolving in the orthogonal direction. However, in vivo experimental data show that four-fold vertices can remain stable for long times, raising the question of how cellular tensions are remodeled to ensure the stability of higher-order vertices and their eventual splitting into tricellular vertices. Existing vertex-based models of confluent tissues with constant and uniform tension are unable to account for the observed phenomena. We, therefore, present a new dynamic vertex model of epithelial tissues, where the tension in the intercellular junction is remodeled depending on the magnitude and direction of the local strain. The model demonstrates that tension increase upon contraction and reduction upon extension can induce the stability of higher-order vertices. Furthermore, asymmetric rates of tension remodeling in response to contraction and extension can result in vertex instability and fluid tissues. |
Tuesday, March 7, 2023 5:00PM - 5:12PM |
K10.00011: Competition between activity and shear in biological tissues: yielding, shear thinning and discontinuous shear thickening. Michael Hertaeg, Suzanne M Fielding, Dapeng Bi Biological tissues demonstrate mechanical integrity and solid-like behaviour on short time scales, while exhibiting cellular rearrangements and liquid-like flow over longer time scales. Such complex jamming/unjamming behaviour underpins many important processes, including wound healing, cancer development and morphogenesis. In this work, we study numerically the yielding behaviour of biological tissues using a minimal vertex-based model, in which a 2D layer of confluent cells is represented by a tiling of polygons, defined by the positions of the vertices [1]. When a tissue is in the vicinity of the solid-fluid transition, we find that internal active forces compete with an externally applied shear to produce a host of distinct rheological behaviours, including yielding, shear thinning, continuous shear thickening, and discontinuous shear thickening |
Tuesday, March 7, 2023 5:12PM - 5:24PM Author not Attending |
K10.00012: Probing Dynamic Structure-Function Relationship of Bone at the Nanoscale Ottman Tertuliano Biogenic composite materials such as bone exhibit a combination of properties exceeding that of their constituents, a feat generally credited to their hierarchal structure, down to the nanoscale. Bone is complex tissue with nanoscale mineralized collagen fibrils as mechanical building blocks. Because of the inherent nanometer scale, we have a limited knowledge of time-dependent and small scale bone response to physiological loading. During cycling loading, injury, and repair, bone tissue is exposed to large strains and dynamic loads representing a drastic departure from the quasi-static and macroscale conditions for the which our current knowledge of bone fracture is based. Here, we will employ in situ experimental nanomechanical experiments to tackle: how does the nanostructure of bone respond to cycling physiological loading? and what mechanisms dictate dynamic fracture in bone? |
Tuesday, March 7, 2023 5:24PM - 5:36PM |
K10.00013: Flow and deformation of tumor spheroids through constricted microchannels Pouyan E Boukany The viscoelastic properties of cancer cells play a key role in tumor growth and invasion during metastasis. To understand and ultimately prevent metastasis, we need to understand how tumor cells interact physically with their environment, both as individual cells and collectively. Nowadays, tumor spheroids have become powerful cellular models to investigate the biomechanics of tumors (from stiffness to deformability). There is an urgent need to characterize the viscoelastic features of tumor spheroids (from stiffness to viscosity and deformability) in a high-throughput manner. Recently, we have developed new microfluidics platforms to characterize the mechanical responses of spheroids through a constricted channel. We have demonstrated that many spheroids (~50-80 spheroids) can be aspirated on a chip for multiple runs per day. We have tested this microfluidic device for different types of cells (from healthy to malignant and metastatic cells). Finally, we have found that the deformability and rheology of tumor spheroids can be correlated to the metastatic potential of tumor spheroids. Importantly, these microfluidics platforms were also used to characterize the deformability and plastic response of various spheroids under various flow conditions. We believe that these microfluidic devices allow us to provide new insights into a biophysical understanding of tumorigenesis and mechanically phenotype tumor cells for cancer metastasis. |
Tuesday, March 7, 2023 5:36PM - 5:48PM |
K10.00014: Cell Deformation Signatures along the Apical-Basal Axis: A 3D Continuum Mechanics Shell Model Jairo Martin Rojas Huamaní, Mayisha Z Nakib, William Brieher, Sascha Hilgenfeldt Two-dimensional (2D) mechanical models of confluent tissues have related the mechanical state of a monolayer of cells to the anisotropy or eccentricity of the cell shapes, predicting floppiness or rigidity of the material. For the well-studied system of in-vitro MDCK epithelial cells, however, we find experimentally that cells in mechanically solid tissues display large anisotropy characteristic of a fluid state in 2D models. We hypothesize that this discrepancy is due to mechanical effects in the third (apical-basal) dimension, caused by actin stress fibers near the basal membrane. To fundamentally understand the effect of such additional stress on the shape of a cell, we develop a 3D continuum mechanics model of an epithelial cell as an elastic cylindrical shell, with appropriate boundary conditions reflecting the action of the basal fiber bundles. This formalism yields analytical solutions predicting the resultant cross-sectional shapes at different positions along the cylinder axis. Confocal-slice experimental data confirm the significant and systematic change in cell shape parameters in this apical-basal direction. The approach allows for arbitrary reference cell shapes and takes into account the effect of neighboring cells’ stress states. Its results can be used to augment the 2D modeling with information about the basal fiber stress, explaining the strongly anisotropic cells in rigid tissues and paving the way to a more realistic description of single-layer confluent tissue mechanics. |
Tuesday, March 7, 2023 5:48PM - 6:00PM |
K10.00015: Cell Shape Changes Driven by Actomyosin Contractility Fahmida Sultana Laboni, Makito Miyazaki, Taeyoon Kim A change in cell shapes occurs in various physiological processes. For example, cells undergoing migration or apoptosis transiently form bulges on the membrane called blebs. It has been suggested that the formation and retraction of cell blebs are induced by osmotic pressure and locally weak coupling between the cell cortex and the membrane. To better understand an intrinsic mechanism for bleb formation, we developed an agent-based cell-like model by incorporating our well-established actomyosin network model with a cell membrane simplified into a triangulated mesh. The cortex is coupled to the membrane by allowing a fraction of cross-linkers to bind to the membrane. We identified parametric spaces for bleb formation consisting of myosin density, cross-linking density, and the strength of coupling between the cortex and membrane. We also observed other interesting cell shape changes, such as contractile ring formation, cortical flow, and significant membrane deformation. We verified our computational results by comparing them with in vitro experimental results obtained under similar conditions. Our results provide insights into understanding how cell blebs emerge in physiological processes as well as how cell shapes change due to actomyosin contractility in general. |
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