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 B16: Non-Linear Dynamics in Biological CellsFocus Live
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Sponsoring Units: GSNP DBIO Chair: Samuel Safran, Weizmann Institute of Science |
Monday, March 15, 2021 11:30AM - 11:42AM Live |
B16.00001: Local thermodynamics governs the formation and dissolution of protein condensates in living cells Anatol W. Fritsch, Andres Diaz, Omar Adame-Arana, Carsten Hoege, Anthony A Hyman, Frank Julicher, Christoph Weber The spatial organization of cells is characterized in part by chemically distinct membraneless compartments known as condensates. A well-studied example of condensates are P granules in the roundworm C. elegans which play an important role in the determination of the germ line. P granules are RNA-rich protein condensates which share the key properties of liquid droplets such as the spherical shape, the ability to fuse, fast diffusion of molecular components. A remaining question is to what extend an equilibrium thermodynamic picture is appropriate to describe the formation of condensates in an active cytoplasm. To address this question, we investigate the response of P granule condensates in living cells to temperature changes as a thermodynamic perturbation. We observe that P granules dissolve upon increasing the temperature and recondense upon lowering the temperature in a reversible manner. Strikingly, this temperature response can be captured by a thermodynamic Flory-Huggins model. Together with the previously characterized droplet properties of P granules our findings provide strong evidence that P granules assembly and disassembly are governed by phase separation based on local thermal equilibria embedded in larger scale non-equilibrium conditions of a living cell. |
Monday, March 15, 2021 11:42AM - 11:54AM Live |
B16.00002: Active Volume Regulation in Adhered Cells Ram Adar, Samuel Safran Recent experiments reveal that the volume of adhered cells is reduced as their basal area is increased. During spreading, the cell volume decreases by several thousand of cubic micrometers, corresponding to large pressure changes of the order of MPa. We show theoretically that the volume regulation of adhered cells is determined by two concurrent conditions: mechanical equilibrium with the extracellular environment and a generalization of Donnan (electrostatic) equilibrium that accounts for active ion transport. Spreading affects the structure and hence activity of ion channels and pumps, and indirectly changes the ionic content in the cell. We predict that more ions are released from the cell with increasing basal area, resulting in the observed volume–area dependence. Our theory is based on a minimal model and describes the experimental findings in terms of measurable, mesoscale quantities. We demonstrate that two independent experiments on adhered cells of different types fall on the same master volume–area curve. Our theory also captures the measured osmotic pressure of adhered cells, which is shown to depend on the number of charged molecules that are confined to the cell, their charge, and their volume, as well as the ionic content. |
Monday, March 15, 2021 11:54AM - 12:06PM Live |
B16.00003: Coarse-grained Modeling of Centrosome Oscillation Yuan-nan Young, Reza Farhadifa, Michael Shelley Centrosome positioning and dynamics are an important part of mitotic spindle formation during cell division. In this talk we present theoretical modeling of centrosome oscillation due to the collective attachment/detachment of cortical force generators to astral microtubules emanating from the centrosome. Focusing on a stoichiometric model for the collective pulling force from the microtubules on the centrosome, we conducted both linear analysis and weakly nonlinear calculations to identify (a) the condition for centrosome oscillation, (b) parameters for stable nonlinear periodic orbits, and (c) oscillation periods of the stable periodic orbits. Full spectral simulations of the stoichiometric model illustrate interesting nonlinear dynamics beyond the weakly nonlinear regime, and provide insight into how noises couple to nonlinear oscillations in the stochastic simulations. These results also provide means to estimate the conditions in biological experiments in the laboratory. |
Monday, March 15, 2021 12:06PM - 12:18PM Live |
B16.00004: Computational model for cell motion on asymmetric surfaces Corey Herr, Igor S Aronson, Wolfgang Losert Cell motility – the ability for a cell to move spontaneously from one location to another – provides a difficult challenge for computational modelling. Cell motility is essential for biological processes such as embryonic development, immune response, and wound healing. However, the interplay between the signaling proteins that control motility and the deformable boundary of a cell have not been captured in previous models. We have created a three-dimensional, physics-based model to describe cell motility that links a deformable boundary to an actin polarization vector field. The model can account for a variety of surrounding topography, including surfaces with features much smaller than the scale of the cell. In agreement with experiments, the model shows spontaneous polarization of cells on asymmetric surfaces. Additionally, we reproduced unidirectional guidance of cells on the ‘sawtooth’ surface that occurs in experiments and show a transition in guidance direction as model parameters change. These findings demonstrate that our model has predictive properties for cell dynamics on complex surfaces. |
Monday, March 15, 2021 12:18PM - 12:30PM Live |
B16.00005: Understanding the underlying mechanisms of pattern formation and cellular aggregation Debangana Mukhopadhyay, Rumi De One of the most fundamental issues in developmental biology is the ability of cells to form tissues. Here we employ a lattice model to study the structure formation of cellular aggregates regulated through different mutually attractive forces. Aggregation of cells on a two-dimensional monolayer substrate consists of a series of motility, collision, and different adhesion processes to form tissues. Here we present a model with three different cellular interactions, ie, cell adhesion via physical contact, mechanical and chemotactically driven motility to investigate the growth of collective cellular structures. Using specific substrate rigidity, our simulation reveals that in the presence of chemotaxy, the mean cluster size and number of clusters vary significantly than the other two interactive forces. Moreover, our simulations also capture several dynamical properties of growing aggregates, such as rate of cell aggregation, correlation function, cluster size distribution, and compactness of the aggregates. Interestingly the dynamical cluster domain growth is represented by a power law in which the exponents remain identical in any conditions. The size distributions of clusters are qualitatively discussed in terms of stretched exponentials which is lost in chemotaxy. |
Monday, March 15, 2021 12:30PM - 12:42PM Live |
B16.00006: Modeling the dynamics of furrow ingression in Drosophila cellularization CAN UYSALEL, Anna Marie Sokac, PADMINI RANGAMANI During Drosophila cellularization, which is the first cytokinetic and tissue building event in Drosophila embryos, a membrane reservoir stored in the form of microvilli unfolds to fuel cleavage furrow ingression. Experiments have demonstrated that furrow ingression is kinetically coupled to the loss of surface area of the microvillar reservoir and that furrow ingression takes place in two kinetic phases. In this work, we developed a quantitative biophysical model of the dynamics of furrow ingression. Our model is based on principles of force balance where plasma membrane tension, cytoskeletal force generation, and force generated by motor proteins (number and force per protein) play important roles in the kinetics of furrow ingression. Each of the force generating terms is informed by known biophysical mechanisms. The resulting governing equations from the model are able to capture the key dynamics of furrow ingression as observed by experiments. In addition, we introduced in silico variations of the key biophysical parameters, including membrane tension and number of motor proteins, and found that the total membrane area available in the microvillar reservoir is a key determinant of the kinetics of furrow ingression. |
Monday, March 15, 2021 12:42PM - 12:54PM Live |
B16.00007: Extreme antagonism arising from gene-environment interactions Thomas Wytock, Manjing Zhang, Adrian Jinich, Aretha Fiebig, Sean Crosson, Adilson E Motter Antagonistic interactions in biological systems, which occur when one perturbation blunts the effect of another, are typically interpreted as evidence that the two perturbations impact the same cellular pathway or function. Yet, this interpretation ignores extreme antagonistic interactions wherein an otherwise deleterious perturbation compensates for the function lost due to a prior perturbation. Here, we report on gene-environment (GxE) interactions involving mutations that are deleterious in a permissive environment but beneficial in a specific environment that restricts growth. These extreme antagonistic interactions constitute GxE analogs of synthetic rescues previously observed for gene-gene interactions. Our approach uses two independent adaptive evolution steps to address the lack of experimental methods to systematically identify such extreme interactions. We successively adapt Escherichia coli to defined glucose media without and with the antibiotic rifampicin, revealing multiple mutations that are beneficial in rifampicin's presence and deleterious in its absence. This work facilitates the systematic characterization of extreme antagonistic gene-drug interactions, which can be used to identify targets to select against antibiotic resistance. |
Monday, March 15, 2021 12:54PM - 1:06PM Live |
B16.00008: SiGMoiD: A superstatistical generative model for binary data Purushottam Dixit In modern biological physics, there is a great interest in building generative probabilistic models for ensembles of covarying binary variables. A popular approach is to use the maximum entropy principle. Here, one builds generative models that use as constraints lower level statistics estimated from the data. While extremely popular, maximum entropy models have conceptual as well as practical issues; they rely on the modelers9 choice of constraints and are computationally expensive to infer when the number of variables is large (n > 100). Here, we address both these issues with Superstatistical Generative Model for Binary Data (SiGMoiD). SiGMoiD is a maximum entropy based framework where we imagine that the data as arising from superstatistical system; individual binary variables are coupled to the same bath whose intensive variables fluctuate from sample to sample. Moreover, instead of choosing the constraints, in SiGMoiD we choose only the number of constraints and let the algorithm infer them from the data itself. Notably, we show that SiGMoiD is orders of magnitude faster than current maximum entropy-based models and allows us to model collections of very large number of binary variables. We also discuss future directions. |
Monday, March 15, 2021 1:06PM - 1:42PM Live |
B16.00009: Loop extrusion, chromatin crosslinking, epigenetics, and the geometry, topology and mechanics of chromosomes and nuclei Invited Speaker: John Marko The chromosomes of eukaryotic cells are based on tremendously long DNA molecules that must be replicated and then physically separated to allow successful cell division. I will discuss what we have learned about chromosome structure from our group's biophysical experiments and mathematical modeling of chromosome structure. A key emerging feature of chromosome organization is the role of active chromatin loop formation, or "loop extrusion" as a mechanism leading to chromosome compaction, individualization, and segregation. I will discuss our work on physics-based modeling of the SMC complexes thought to be the loop-extruding elements. I will also discuss our group's studies of the role of chromatin and epigentic mark-crosslinking "readers" in control of global structure and integrity of the interphase nucleus. We have found that disruption of elements key to heterochromatin - specifically histone H3K9 methylation or levels of the heterchromatin protein HP1α - leads to weakening, shape destabilization, and rupture of nuclei, indicating a structural role for heterochromatin in maintaining normal nuclear organization. |
Monday, March 15, 2021 1:42PM - 1:54PM Live |
B16.00010: Transport, Delivery, and Kinetics in Tubular Organelle Networks Zubenelgenubi C Scott, Aidan Brown, Elena Koslover The endoplasmic reticulum (ER) forms an interconnected tubular network that plays a crucial role in cell functions ranging from protein quality control to calcium signalling. These functions require proteins to move within the networked architecture in order to find their binding partners. We leverage physical modeling, combined with analysis of live-cell imaging data, to investigate the transport of particles confined within a tubular network. We have developed new methods for efficient numerical simulations of diffusive network transport, for exact calculations of mean first passage times, and for analysis of dynamic experimental data such as single particle trajectories and spreading of photoactivated probes. |
Monday, March 15, 2021 1:54PM - 2:06PM Live |
B16.00011: Criticality in optimal organelle biogenesis Fang Yu, Shankar Mukherji Among the hallmarks of the eukaryotic cell is its organization into organelles. In order to tailor organelle biogenesis to the needs of the cell, the cell can regulate the size and number of many of its organelles. Organelle biogenesis, however, is fundamentally constrained by the limited available pool of resources available to the cell to synthesize its organelles. What principles dictate how much of the cell’s limited resources are devoted to increasing the number versus the size of a given organelle? This question can be cast in terms of the NP-hard mixed integer nonlinear optimization. Here we propose a model of resource allocation to organelle number and size and use the tools of MINLOP to solve for optimal organelle number and size subject to the constraint of having only a limited pool of resources to build organelles from. We find that the solutions to the constrained optimization fall into two regimes separated by a critical point, suggesting that cells face an unexpectedly sharp tradeoff between organelle number and size in resource-limited contexts. The existence of this critical point is consistent with observations that cells grow larger numbers of small organelles as opposed to simply reducing each organelle’s size when faced with a constraining pool of resources. |
Monday, March 15, 2021 2:06PM - 2:18PM Live |
B16.00012: Theoretical framework for the description of transmembrane receptor cluster coalescence in cells Kathrin Spendier, Vasudev M Kenkre Moving boundary problems that appear in many fields of science are notoriously difficult to formulate and solve. Due to their complexity, approximation methods play an important role and are widely used to analyze such systems. We present an approximation method for moving boundaries or traps in reaction-diffusion processes that is applied to investigate coalescence of receptor clusters in mast cells. To handle the complexity, which stems from boundary growth due to particle melding, the study is divided into three parts. The first is about stationary trapping problems investigated by the standard defect technique, and the second is about a validity study of an adiabatic approximation for moving boundaries. In the last part, a coalescence theory is developed, which is based on a completely self-consistent approach. Finally, the developed theoretical framework is applied to study the kinetics of immunoglobulin E receptors (FcεRI) cluster coalescence in rat basophilic leukemia cells. |
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