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 X11: Mechanics of Cells and Tissues VFocus Live
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Sponsoring Units: DBIO DSOFT Chair: Chase Broedersz, VU Univ Amsterdam and LMU Munich; Pierre Ronceray, Princeton University |
Friday, March 19, 2021 8:00AM - 8:36AM Live |
X11.00001: Frustration and compromise in collectively moving cell clusters Invited Speaker: Ajay Gopinathan Mechanically coupled, migrating clusters of cells mediate a variety of critical physiological processes such as embryonic development, wound healing and cancer metastasis. In this talk, I shall describe a few examples of our work on modeling such clusters, highlighting how frustration can arise at the group level because of heterogeneity in behavior among members of the cluster. I shall show how such frustrations may be resolved leading to new collective phases of motion. I shall connect our results to experimental observations of malignant lymphocytes undergoing chemotaxis showing that such phases can be functionally important – enabling, for example, robust chemotaxis and “load sharing” among cells in the cluster. |
Friday, March 19, 2021 8:36AM - 8:48AM Live |
X11.00002: Learning the dynamics of cell-cell interactions in confined cell migration David Brückner, Nicolas Arlt, Alexandra Fink, Pierre Ronceray, Joachim Rädler, Chase Broedersz In many physiological processes, contact-mediated cell-cell interactions play a key role in shaping the stochastic trajectories of migrating cells. However, a quantitative framework to describe the stochastic dynamics of interacting cells in remains elusive. Here, we monitor stochastic cell trajectories in a minimal experimental cell collider: a dumbbell-shaped micropattern on which pairs of cells perform repeated cellular collisions. We observe different characteristic behaviors, including cells reversing, following and sliding past each other upon collision. Capitalizing on this large experimental data set of coupled cell trajectories, we infer an interacting stochastic equation of motion that accurately predicts the observed interaction behaviors. Our approach reveals that interacting non-cancerous MCF10A cells can be described by repulsion and friction interactions. In contrast, cancerous MDA-MB-231 cells exhibit novel and surprising attraction and anti-friction interactions, promoting the predominant relative sliding behavior observed for these cells. Based on these experimentally inferred interactions, we show how this framework may generalize to provide a unifying theoretical description of the diverse cellular interaction behaviors of distinct cell types. |
Friday, March 19, 2021 8:48AM - 9:00AM Live |
X11.00003: Modeling cell motility at mechanical interfaces Subhaya Bose, Patrick Noerr, Arvind Gopinath, Kinjal Dasbiswas Many animal cells crawl by adhering to and exerting active mechanical forces on elastic extracellular substrates. Experiments with adherent cells show that cells align preferentially at interfaces between soft and stiff regions of the substrate resulting in durotaxis. We use agent-based Brownian dynamics simulations to study the mechanical interactions between motile cells. The cells are modeled as self-propelling agents that exert active force dipoles on the substrate leading to inter-cell and cell boundary interactions. Elastic effects at the interface between soft and stiff regions of the substrate are simulated using appropriate clamped or free boundary conditions. We find that torques due to these boundary interactions strongly align crawling cells at the interface analogous to hydrodynamic torques on swimming bacteria. We systematically investigate the collective motility and density distributions of a collection of model cells that result from these interfacial elastic interactions. We then compare quantitative structural metrics of the patterns that ensue in these systems with full interactions to simulations of cells that interact elastically with the boundary but not with each other. |
Friday, March 19, 2021 9:00AM - 9:12AM Live |
X11.00004: Recursive Feedback Between Matrix Dissipation and Chemo-mechanical Signaling Drives Oscillatory Growth of Cancer Cell Invadopodia Ze Gong, Katrina M Wisdom, Eoin McEvoy, Julie Chang, Kolade Adebowale, Ovijit Chaudhuri, Vivek b Shenoy Most extracellular matrices (ECMs) are known to be dissipative, exhibiting viscoelastic and often plastic behaviors. However, the influence of dissipation on cell motility, in particular the plasticity in 3D environments that endows matrix with long-term mechanical memory, is not clear. Here, we develop a chemo-mechanical model to predict the impact of matrix plasticity on the dynamics of invadopodia, the protrusive structures that cancer cells use to facilitate invasion. We show that matrix dissipation facilitates invadopodia oscillations by softening the ECMs over repeated cycles, during which plastic deformation accumulates via cyclic ratcheting. Our model reveals that distinct patterns of protrusion behavior, oscillatory or monotonic, emerge from the interplay between extension-associated viscosity and signaling-associated myosin recruitment. We also predict and experimentally validate the influence of different drug treatments on invadopodia dynamics. More importantly, our model provides a quantitative framework to understand how ECMs can serve as a memory storage mechanism for protrusions that is “written on” or “read” by cells. |
Friday, March 19, 2021 9:12AM - 9:24AM Live |
X11.00005: Not only proteins: The role of compressed sugars in cell migration Shlomi Cohen, Patrycja Kotowska, Patrick Chang, Yu Jing, Rebecca Keate, Dennis Zhou, Andres Garcia, Shuyi Nie, Jennifer E. Curtis <div style="direction: ltr;">Cells use adhesion complexes to bind to the extracellular matrix. Extending up to tens of nanometers from the membrane, these molecular adhesions are often embedded within the much thicker hyaluronan-rich glycocalyx, a bulky polymeric structure comprised of high molecular weight membrane-associated hyaluronan chains. Our theoretical estimates indicate that a significant mechanical loading of adhesion bonds arises from compressed glycocalyx at the cell- extracellular matrix interface. In this work, we study three cell types to address the mechanics of cell adhesion in the presence of hyaluronan-rich glycocalyx, with a focus on its implications for cell migration. Measurements of the interfacial gap at the cell substratum, glycocalyx-dependent cell adhesion strength and migration speed are combined with quantification of adhesions and characterization of their spatial organization within the glycocalyx. Together, these data provide strong evidence for a mechanical role of the glycocalyx in mediating cell adhesion and migration.</div> |
Friday, March 19, 2021 9:24AM - 9:36AM Live |
X11.00006: VELOMIR: Fast microrheology sensor with high temporal and spatial resolution reveals onset of drug effects on single cell level Jonas Pfeil, Daniel Geiger, Tobias Neckernuss, Othmar Marti Continuous high speed, high precision video tracking of particles is challenging due to the associated data rates. This currently limits passive and active microrheology to short tracking times and sophisticated setups. We present VELOMIR, VEry LOngtime MIcroRheology, a compact tool that tracks multiple particles in real time with up to 10 kHz sampling rate for almost infinite long tracking times. It uses a CMOS sensor tightly coupled with an FPGA to achieve real-time data processing. This captures the microrheological properties of biological tissue and cells with a dynamic range of up to 8 decades. Despite this remarkable increase, we show that the precision of the sensor is comparable to that of current systems. By analyzing short time slices, we show the time evolvement of drug-induced changes in viscoelastic properties of adherent living cells over long timespans in the hour-range. This technology will enable faster testing of the effectiveness of some drugs and better characterization of their effects. |
Friday, March 19, 2021 9:36AM - 9:48AM Live |
X11.00007: Myosin motors regulate Drosophila stretch receptors Chonglin Guan, Kengo Nishi, Christian Kreis, Oliver Baeumchen, Martin C. Goepfert, Christoph F. Schmidt Insects sense vibrations and body movements with chordotonal organs, specialized stretch receptors that monitor relative motion between body parts. We have performed a combination of electrophysiological and micromechanical experiments on living lch5 organs of Drosophila larvae. These chordotonal organs are pre-tensioned by accessory cap cells. We found that the extracellular matrix surrounding the cap cells maintains the basic resting tension. The extremely elastic cap cells contain microtubules, actin structures, and nonmuscle myosin-II motors. We found that myosin-II motor activity drives cap cell contraction and is involved in sensory adaptation. Optogenetic activation of myosin-II in the cap cells induced contractions and triggered spiking responses of the mechanoreceptors. Cap cell-specific knockdown of the regulatory light chain of myosin-II lowered tension in the chordotonal organs, decreasing the cap cell elastic modulus. Along with these mechanical effects, mechanoreceptor responses became more tonic, reflecting alterations in spiking synchronicity and mechanosensory adaptation. |
Friday, March 19, 2021 9:48AM - 10:00AM Live |
X11.00008: Correlation Studies of Cells' Velocimetry on Micropatterned Substrates Keontré I Hughes, Nicholas G Hallfors, Jeremy Teo, Abdel F. Isakovic We analyzed the cells kinematics on micropatterned substrates using cells velocimetry and fluorescence microscopy for human foreskin fibroblast (HFF) cells. Analysis of the displacement as a function of the square root of time leads to the identification of several qualitatively different modes of transport. We observe a broad range of kinematic options exploited by the cells, including some large range rotational motion, depending on the detailed nature of the microfabricated silicon substrate. It is of particular interest to note that the cells motion on highly structured, periodic substrates provides qualitatively different kinematics data than the motion on randomly patterned substrates. Naturally, both of these patterned substrates lead to different motion than the motion on pristine, low surface roughness substrates. In order to better quantify various motility modes, we analyze position-position, position-velocity, and velocity-velocity correlations. These appear to support our experimental observation that two main phenomena are in play – interaction of cells with the substrate and cell-cell interaction. |
Friday, March 19, 2021 10:00AM - 10:12AM Live |
X11.00009: Dynamic Mechanotransductive Self-Reinforcement of Transcription Factors Induces Memory of Gene Expression Chris Price, Jairaj Mathur, Amit Pathak, Vivek b Shenoy Cells adjust to their environment through mechanotransduction, which describes changes in chemical pathways and cell structure to mechanical cues. Recent experiments have shown that transcription factors which regulate gene expression, such as YAP, RUNX2, and miR-21, can exhibit memory of the cell’s environment over time scales of days to weeks. If cultured on an initially stiff (soft) substrate for enough time (priming phase), the cell maintains altered transcriptional activity after the substrate is switched (cooling phase) to soft (stiff) compared to controls. We develop a dynamic self-reinforcement model, posed as a series of Waddington landscapes, to explain mechanical memory during cooling which depends on the priming time and the priming stiffness. Memory naturally emerges beyond the threshold of a critical priming stiffness and a critical level of self-reinforcement. This matches experimental data for osteogenic transcription factors, and we identify biological positive feedback relationships which correlate with the model. The model only assumes mechanosensitive gene expression and both slow and fast dynamics in the cell. Predicting non-linear, hysteretic cell dynamics can be used advantageously to design drug programs which maximize the effect-to-dose ratio. |
Friday, March 19, 2021 10:12AM - 10:24AM Live |
X11.00010: WKB solutions to the wave equation for the cochlea and for acoustic rainbow sensors Riccardo Marrocchio, Angelis Karlos, Stephen Elliott The WKB method is used to derive an approximate solution to the cochlear wave equation, which results from the interaction between the passive dynamics of the basilar membrane and the 1D fluid coupling in the scalae, including both fluid viscosity and compressibility. The resulting WKB solution can be expressed in terms of a few nondimensional parameters, and their physical meaning is discussed. Notably, a nondimensional phase parameter, N, changes the nature of the resonance, which is symmetric for low values of N, indicating weak fluid coupling, and asymmetrical, with a characteristic peak, for high values of N, indicating strong fluid coupling. On the other hand, the contribution from nondimensional parameters derived from the fluid viscosity and fluid compressibility is negligible. It is then shown that recent designs of acoustic rainbow sensor, comprised of an array of Helmholtz resonators of increasing size coupled to a duct, are described by a wave equation which has the same form of that of the cochlea. However, in this case, the nondimensional compressibility parameter is much larger than in the cochlea, and so plays a more dominant role in determining the response. |
Friday, March 19, 2021 10:24AM - 10:36AM Live |
X11.00011: DNA Supercoiling Drives the Switch between Long-range Cooperative and Antagonistic RNAP Dynamics Purba Chatterjee, Nigel Goldenfeld, Sangjin Kim Recent experiments demonstrate that while co-transcribing RNAPs cooperatively increase their efficiency in the active state of the promoter, environmentally induced promoter repression results in long distance antagonistic interactions that drastically reduces RNAP speeds and causes quick synthesis arrest of mRNA. What mechanism underlies this switch between cooperative and antagonistic dynamics? Here we introduce a continuum deterministic model for RNAP translocation where the elongation velocity of an RNAP is coupled to the local supercoiling and RNAP density. Crucial to the model is the hypothesis that transcription factors act as physical barriers to supercoil diffusion, which explains the dependence of gene expression efficiency on the state of the promoter. We show that this simple model exhibits two transcription modes mediated by the supercoiling stress, a fluid mode when the promoter is ON, and a torsionally stressed mode when the promoter is OFF, in good qualitative agreement with experimentally observed dynamics of co-transcribing RNAPS. |
Friday, March 19, 2021 10:36AM - 10:48AM Live |
X11.00012: Biophysical modeling of membrane-actin interactions governing the morphology of dendritic spines Haleh Alimohamadi, Miriam Bell, Shelley Halpain, Padmini Rangamani Dendritic spines are primary excitatory postsynaptic sites and are associated with characteristic shapes. While it is well known that dendritic spines are rich in actin and have a complex cytoskeletal organization that aids in their function, how actin forces and membrane mechanics contribute to dendritic spine morphology from a mechanical standpoint remains poorly understood. In this study, we developed a minimal biophysical model to investigate the role of membrane-actin interactions in governing dendritic spine geometries. We identified the relationship between heterogeneous actin-mediated forces and tension necessary to reproduce the characteristic range of dendritic spine protrusions. We were also able to compare our analytical solutions to our numerical simulations with high degrees of agreement and provide scaling laws between different biophysical characteristics. A key result from this work is that we showed the cooperation between different mechanisms provides various mechanical pathways to sustain different spine shapes and found that some mechanisms may be energetically more favorable than others. We believe our findings provide a framework for the experimental and computational investigation of dendritic spine size and shape due to heterogeneous force distributions. |
Friday, March 19, 2021 10:48AM - 11:00AM Live |
X11.00013: Investigating Bacterial Deformation Upon Surface Attachment Using Finite Element Modeling Yu-Chern Wong, Vernita Gordon Bacteria adhere to different surfaces and, upon sensing the surface, transition to a biofilm state. Studies have shown that bacteria sense a mechanical cue upon surface adhesion, resulting in deformation of the cell envelope that can be transduced by mechanosensitive proteins. Direct experimental measurement of nanoscopic deformation in micron-scale bacteria is difficult. Hence, we develop finite element modeling to estimate the bacterial deformations due to adhesion. We model bacteria as thin-walled pressure vessels, using physical properties reported in the literature, that adhere to substrates via a van der Waals force. By varying shape, physical properties, and envelope thickness, we can model attachment mechanics of different bacterial strains. Particularly we explore P. aeruginosa (rod-shaped; Gram-negative), B. subtilis (rod-shaped; Gram-positive), and S. aureus (spherical; Gram-positive). We expect this modeling to shed light on mechanisms of and potential for surface sensing. For example, we find that attachment to a rigid surface can increase normal stress on the P. aeruginosa cell envelope by one order of magnitude. This, and the corresponding thinning of the envelope, likely give rise to surface sensing. |
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