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 A18: Non-Linear Dynamics in Cell MechanobiologyInvited Live
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Sponsoring Units: GSNP Chair: Phil Nelson, University of Pennsylvania |
Monday, March 15, 2021 8:00AM - 8:36AM Live |
A18.00001: Active Cell Nematics: Architectures and flows Invited Speaker: pascal silberzan When cultured in monolayers, spindle-shaped cells such as NIH-3t3 fibroblasts form domains of common orientation whose characteristic size (~ 500 µm) is very large compared to a cell size. These domains don’t fuse because of the presence of intrinsic topological defects characteristic of these 2D nematic phases. Confining these fibroblasts in mesoscale stripes whose width is smaller than this length results in a defect-free nematic ordering whose director aligns with the stripe’s direction. However, in the same confinement condition, more active cell types such as myoblasts adopt a more complex nematic architecture by spontaneously orienting at a finite angle with respect to the stripe direction, and developing a shear flow. This situation is reminiscent of in vivo observations where cancer cells escaping collectively from a tumor can locally migrate in antiparallel directions within the same strand. Cell types characterized by an even higher activity show hallmarks of turbulence. Confining the cells in circular domains imposes a topological charge that results in a pair of defects whose position indicates that, at high cell density, activity is eventually overcome by friction with the underlying substrate. Finally, myoblasts don’t remain as monolayers but eventually form multilayers. We show that this multilayering process is initiated at defects and is made possible by the secretion of Extra Cellular Matrix by the cells. Because of the architecture of the cells near the core of the defect, successive layers are perpendicularly oriented as it is often the case for muscle tissues in vivo. |
Monday, March 15, 2021 8:36AM - 9:12AM Live |
A18.00002: Non-linear dynamics and long-time phase correlations of beating cardiomyocytes Invited Speaker: Samuel Safran The observation of spontaneous calcium oscillations of ~ 1Hz in isolated, beating cardiac cells is typically explained by many coupled chemical reactions and parameters. We show that the separation of time scales of fast processes with slower calcium diffusion in the cell results in a single, non-linear dynamical equation that characterizes these oscillations with only a few physically relevant parameters, determined from independent experiments. The beating phase is related to the time-dependent deviation of the oscillations from their average frequency, due to noise and the resulting cellular response. Here, we demonstrate experimentally that in addition to the short-time (1-2 Hz), beat-to-beat variability there are long-time correlations (tens of minutes) in the beating phase dynamics of isolated cardiomyocytes. Our theoretical model relates these long-time correlations to cellular regulation that restores the frequency to its average, homeostatic value in response to stochastic perturbations. This defines a new mesoscaopic time scale in cardiac cell beating, which we call the regulation time. |
Monday, March 15, 2021 9:12AM - 9:48AM Live |
A18.00003: Chromosome folding by loop extrusion on busy genome Invited Speaker: Leonid Mirny We will review our recent progress in understanding loop extrusion and its interference with other biological processes on DNA. First, we will discuss how the process of transcription can serve as a directional boundary to extrusion. A model where loop-extruding factors can bypass a polymerase after some pausing can explain a broad range of data from bacterial and eukaryotes. Second, we will show the effect of random barriers on loop extrusion and provide evidence that such barriers are abundant in the cell. Third, we will show new experimental data which indicate that loop-extruding factors can bypass each other when they meet. Together, these results suggest that loop extruding factors can bypass a variety of obstacles. We posit that the bypassing activity enables SMC complexes to spatially organize a functional and busy genome. |
Monday, March 15, 2021 9:48AM - 10:24AM Live |
A18.00004: Mechanics of Phase Separation in, on, and around the Genome Invited Speaker: Cliff Brangwynne In this talk I will discuss our work to understand and engineer intracellular phase transitions, which play an important role in organizing the contents of living cells. Membrane-less RNA and protein rich condensates are found throughout the cell, and regulate the flow of genetic information. This functional role is particularly important in the nucleus, where phase separated condensates form in, on, and around chromatin, a complex polymeric material which stores information and controls gene expression. However, the way in which chromatin impacts the dynamics of phase separation is poorly understood. We have recently demonstrated that droplet growth dynamics are directly inhibited by the chromatin-dense environment, which gives rise to an anomalously slow coarsening exponent, β≈0.12, contrasting with the classical prediction of β≈1/3. This arrested growth can arise due to subdiffusion of individual condensates, with a theoretical prediction of β=α/3, where α is the diffusive exponent, in good agreement with the measured subdiffusive exponent of α≈0.5. I will discuss the implications of these findings for genomic structure and function, and ongoing work to use condensates as probes of the viscoelastic environment within living cells. |
Monday, March 15, 2021 10:24AM - 11:00AM Live |
A18.00005: Effect of Cyclic Strain on Cardiomyocytes and Fibroblasts and Its Relation to Heart Disease Invited Speaker: Ana Grosberg The heart is a dynamic mechanical environment, and both cardiomyocytes and fibroblasts play an important role in myocardium function. Both the mechanics and cell composition of the myocardium changes in pathology. The interplay between the cell phenotype and mechanical stimulation needs to be considered to understand the biophysical cell interactions in healthy and diseased myocardium. The design is challenged by the different response of fibroblasts and cardiomyocytes to the cyclic stretching. Indeed, in isolation the fibroblasts orient perpendicular to cyclic strain, while the cardiomyocytes will align parallel. This is in contradiction to the cellular architecture in a healthy heart. In this work, we hypothesized that the dominant cell type dictates the overall tissue organization in the heart, which would explain the tendency toward disorganization in fibrotic regions of the heart. To test this, the cardiomyocytes and fibroblasts were co-cultured at different ratios in a cyclic stretcher that mimicked the dominant mechanical strain of the heart. Image processing software was designed to analyze the cytoskeleton architecture of the two cell types separately. The overall and local organization was evaluated using the orientational order parameter and compared among all conditions. The cardiomyocytes and fibroblasts were found to orient perpendicular to each other if there was no cell-to-cell contact. Conversely, they were found to influence each other’s orientation in a confluent co-culture. The cells likely influence each other through both mechanical coupling over adherens junctions and physical space limitations. These results elucidate some of the reorganization observed pathologically when fibroblasts dominate a portion of the myocardium. |
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