Bulletin of the American Physical Society
APS March Meeting 2018
Volume 63, Number 1
Monday–Friday, March 5–9, 2018; Los Angeles, California
Session V51: Biophysics of Cellular Organization and Dynamics Across Multiple Spatial Scales - IIFocus
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Sponsoring Units: DBIO GSNP Chair: Moumita Das, Rochester Institute of Technology Room: LACC 511C |
Thursday, March 8, 2018 2:30PM - 3:06PM |
V51.00001: Developing microtissue-building toolbox to study biophysical effects at multiple scales Invited Speaker: Yun Chen Despite the widely acknowledged notion that biophysical properties of the microenvironment are integral in maintaining tissue homeostasis or disease development, it is still technically challenging to study cell dynamics in vitro, with well-defined biophysical parameters such as geometry, stiffness, porosity, micro-organization of the extracellular matrix, and water permeability. We have developed a toolbox to grow microtissues with desired biophysical parameters described above. First, we can combine 3D printing and soft lithography to form epithelium-lined channels with varied radii at sub-100 µm scale. Secondly, we can apply micro-molding techniques and modulate polymer swelling to form capillary-like structures. Third, by using stereolithography to crosslink photo-curable, cell-laden biopolymers such as functionalized gelatin, alginate or collagen, we can fabricate micro-tissues with specific porosity, stiffness and shapes. Fourth, we have devised a self-induced rolling membrane platform, where rectangular thin elastic films are rolled cylindrically by strain mismatching between the two sides of the film, to study the effect of continuum curvature on subcellular organization in the epithelium.Using the toolbox, we are able to build microtissues and made following observations: E-cadherin and ZO-1 expression in the epithelium varies depending on the curvature; cortical actin assembly is associated with tissue geometry and cell-cell adhesion; the steady-state response of the epithelium to hydrostatic pressure perturbations is independent of ECM elasticity but dependent on its porosity and its extent of crosslinking. |
Thursday, March 8, 2018 3:06PM - 3:18PM |
V51.00002: Tumor Printing in Microgels Samantha Marshall, Thomas Angelini, Steve Ghivizzani, Glyn Palmer, W. Sawyer Most of the current understanding of cellular functions comes from research performed in 2D. While 2D studies have led to important pharmacological discoveries, it is important to understand that within the body cancer cells grow in a 3D context. Mouse models are a powerful method for drug screening but widespread use is hindered by high cost, long engraftment periods, and low engraftment rates. Developing 3D culture methods will bring greater understanding of the effects of drugs in a more relevant manner and can effectively bridge the gap between the patient and the dish. While promising, drawbacks of many current 3D culture methods include: the challenge to control size and shape, the requirement for large cell numbers, and the inability for all cell types to aggregate on their own. To alleviate these limitations, jammed granular microgels are used as support baths, allowing 3D printing of cancer cells and observation of interactions in 3D. This method enables mass culture of tumoroids, and provides an opportunity for co-culture and in vitro imaging. With the precise control offered by the 3D printer, arrays of identical shapes can be produced in a variety of sizes and geometries. These shapes can be removed from the microgel for histological sectioning and biochemical assays. |
Thursday, March 8, 2018 3:18PM - 3:30PM |
V51.00003: Using Physical Models of Epithelial Sheets to Study Collective Behaviors of Cells Matthew Heinrich, Andrej Kosmrlj Experiments on epithelial cell sheets reveal many unexplained collective cell behaviors, and simulations offer a promising strategy for understanding how these behaviors arise from cellular level processes. “Active vertex models” are particularly useful because they combine mechanical and migratory properties of cell sheets in a simple framework; we extended these models to include other biological processes. For example, it is not obvious from experiments what causes epithelial tissue to “stick” to a biomimetic boundary coated with E-cadherin; the constituent cells may have maximized their adhesion, lost their migratory drive, or been physically “pinned” to the boundary. Our extended models offer clues for determining what biological processes underlie this behavior. In another experiment, sheets of epithelial cells that are controlled by an external electric field are shown to reverse course via groups of several cells performing independent, coordinated U-turns upon the reversal of the field. We show that this unexpected tissue behavior also emerges in simulated cell sheets by introducing a few simple cell-level rules. In general, this is a powerful approach for making sense of seemingly unexpected experimental results on cell collectives and other multicomponent systems. |
Thursday, March 8, 2018 3:30PM - 3:42PM |
V51.00004: Response of Collective Cell Migration to Surface Topography Reveals Distinct Phenotypes Rachel Lee, Matt Hourwitz, Phillip Alvarez, Keyata Thompson, Michele Vitolo, John Fourkas, Wolfgang Losert, Stuart Martin Migrating cells must respond to a variety of cues from their environment, including many physical forces. A wide range of previous work has focused on the roles of several of these forces in cell behavior, such as how forces between neighboring cells affect collective migration or how the physical properties of the migration substrate affect single cells. In this work, we investigate how multiple forces simultaneously influence migration behavior by imaging collective migration on nano-topographic surfaces. We find that cell lines with varied tumorigenicity balance these physical cues differently, resulting in distinct collective migration behaviors on nano-ridged surfaces. |
Thursday, March 8, 2018 3:42PM - 3:54PM |
V51.00005: Vertex modeling of active superelasticity in epithelial tissues Sohan Kale, Ernest Latorre, Xavier Trepat, Marino Arroyo Epithelial tissues often exhibit 3D shapes during development and physiological functions. However, mechanobiology of epithelial tissues in 3D has not been quantitatively explored. We use epithelial domes developed on soft micropatterned substrates, combined with 3D traction microscopy, to extract constitutive behavior of epithelial tissues. A remarkable plateauing of tissue tension is observed as the domes reach areal strains of up to 300%. While the spherical domes are required to maintain uniform tissue tension, the distribution of cellular strains on the domes is highly heterogeneous as some cells exhibit areal strains close to 1000%. A classical vertex model with constant junctional tensions captures the tensional plateau, but not the strain heterogeneity. We develop a 3D vertex model accounting for cellular-softening induced by cortical depletion and re-stiffening at extreme strains, which captures the contrasting observations of tensional plateau and cellular strain heterogeneity. The model reveals non-convex two-well energy landscape of the cells, which permits co-existence of barely-stretched and superstretched cells to accommodate large strains while maintaining a tensional plateau; all of which are landmark features of superelasticity, albeit, of active origin. |
Thursday, March 8, 2018 3:54PM - 4:06PM |
V51.00006: Planar Cell Polarity in Disordered Tissues: A Model for Robust Long-range Correlations Shahriar Shadkhoo, Madhav Mani Planar cell polarity (PCP) is a highly conserved long-range signaling mechanism that regulates cellular processes in epithelial tissues, including cellular-rearrangements. Long-range PCP is usually already established in a highly disordered tissue, guiding the process of oriented reorganization of cells towards more ordered lattices. Given the detrimental effects of quenched disorder on long-range correlation in condensed matter systems, we ask how PCP survives the static geometrical disorder. In this study, we propose a reaction-diffusion mechanism with nonlocal interactions and show that such a mechanism facilitates the emergence and stability of long-range order of polarization in highly disordered systems. Furthermore, the global orientation of polarization is influenced by a variety of external cues. Elongation is regarded as one symmetry- breaking cue that fixes the orientation of PCP; perpendicular to the elongation axis. We show in this study, how nonlocal interactions can stabilize the distribution of proteins on longer junctions; hence perpendicular polarization, when reaction- diffusion is the dominant mechanism of PCP dynamics. |
Thursday, March 8, 2018 4:06PM - 4:18PM |
V51.00007: Dynamical pattern formation and mode selection on a deformable biological surface Melis Tekant, Tzer Han Tan, Hridesh Kedia, Nikta Fakhri Self-organization of individual units into patterns arises in many biological systems across vast length scales. These ordered structures drive and regulate a plethora of vital biological functions from molecular to ecological level. The study of pattern formation has thus far been limited to surfaces with uniform curvature, even though most biological surfaces are highly non-uniform. Recent theoretical work has shown that by breaking symmetries in these systems, inhomogeneities in the curvature can select for certain patterns. Here, we use cortical Rho activity in starfish oocyte as a model system to explore such effects. In addition to being highly deformable, the oocyte cortex exhibits versatile dynamical chemical patterns that can be tuned. By mapping such patterns onto a two-dimensional sphere using spherical harmonics, we identify the spatio-temporal modes of the pattern, thus revealing the underlying features of the dynamics. By changing the curvature, we can correlate the dynamic features of the pattern with the local curvature perturbation. This framework will allow us to experimentally verify the important role of geometry in pattern formation in biological systems. |
Thursday, March 8, 2018 4:18PM - 4:30PM |
V51.00008: Stochastic Lattice Model of Synaptic Protein Domains on Cell Membranes Everest Law, Yiwei Li, Osman Kahraman, Christoph Haselwandter In chemical synapses, neurotransmitter receptor proteins and their associated scaffolds are found in localized domains, which are complex molecular assemblies. The size, stability and plasticity of these domains play a vital role in modulating signal transmission across chemical synapses. Similar to other types of membrane protein domains, synaptic domains are characterized by crowding and low protein copy numbers. As a result, they exhibit stochastic, collective fluctuations that cannot be explained by mean-field methods. Using kinetic Monte Carlo simulations, we study a stochastic lattice model of the reaction-diffusion dynamics at synaptic domains. For simplicity, only receptors and scaffolds are considered. First and foremost, we have observed the self-assembly of synaptic domains. On this basis, we systematically explore the mechanisms underlying their fluctuations in size, lifetime and molecular occupancy. Our work aims to provide a physical understanding of quantitative experimental data on synaptic domains, which are now available and describe both single-molecular and collective dynamics. |
Thursday, March 8, 2018 4:30PM - 4:42PM |
V51.00009: Influence of Electrotaxis, Chemotaxis and Textured Surfaces on Actin dynamics Sebastian Schmidt, Matt Hourwitz, John Fourkas, Wolfgang Losert Cell migration is integral in many processes such as wound healing and cancer metastasis. Cells can be guided by different types of gradients, for example chemotaxis. We use surfaces with nanotopographical features such as ridges to examine this type of guidance called esotaxis on migration in the well-studied amoeba Dictyostelium Discoideum. In this work we compare chemotaxis with esotaxis on ridges as well as the influence of electrotaxis on the formation of the actin cytoskeleton on these nanotopographies. These esotactic surfaces have more guidance cues for cells than plane 2D cultures and can disrupt other guidance types like chemotaxis. |
Thursday, March 8, 2018 4:42PM - 4:54PM |
V51.00010: Emergence of Collective Oscillation in Adaptive Cell Populations Shou-Wen Wang, Leihan Tang Cell-density-dependent rhythmic behavior, or dynamic quorum sensing, has been suggested to coordinate population level activities such as cell migration and embryonic development. Quantitative study of the oscillatory phenomenon is hitherto hampered by incomplete knowledge of the underlying intracellular processes. Here we show, using tools developed in non-equilibrium stochastic thermodynamics, that robust collective oscillation emerges when individual cells adapt to the signal that mediates cell-to-cell communication. Specifically, we prove a universal ``law'' that the response of an adaptive cell has a phase lead over the external stimulus in certain frequency range, which in turn drives population level cycles when conditions are met. We find this overarching principle to be at work in several natural and synthetic oscillatory systems, and it may help to guide the design of further experiments on glycolytic oscillation in yeast suspensions. |
Thursday, March 8, 2018 4:54PM - 5:06PM |
V51.00011: Dynamics of Injected Nanoprobes in Drosophila Melanogaster Oocytes during Mid-Oogenesis Orin Yue, Justin Bois, Margot Quinlan, Thomas Mason Drosophila melanogaster oogenesis displays a wide range of complex active dynamics over the course of many different stages. We have studied dynamics by injecting fluorescent nanospheres into oocytes during mid-oogenesis and imaging these probes using confocal optical microscopy, which yields sets of particle trajectories. In our analysis, we apply a novel statistical method to quantify the degree of correlated motion in proximate trajectories during stages 9 and 10b. Using these results, we identify local subsets of trajectories that exhibit non-random correlated motion at long times and then apply local collective motion (LCM) analysis. Consequently, we remove the correlated motion and obtain LCM-corrected mean square displacements (MSDs) that describe only the underlying random motion. This random motion is the result of passive Brownian entropic and active motor-driven excitations. Our analyses reveal strongly sub-diffusive behavior dominated by local elasticity in both stage 9 and 10b, but the associated power laws are different. By performing an objective local similarity analysis, we avoid characterizing ensemble averaged probe MSDs as simply convective, diffusive, or bound and reveal changes in local environments in the ooplasm that occur during these different stages. |
Thursday, March 8, 2018 5:06PM - 5:18PM |
V51.00012: Synthesis of monodisperse drug microparticles and high-velocity bombardment as a strategy to traverse epithelial layers and treat pathologies of the cornea Benjamin Laccetti, Julie Kornfield Certain diseases (e.g. Keratoconus) weaken the human cornea, our eyes' protective window and primary focusing lens. Corneal cross-linking therapy (CXL) involves removing the epithelium, applying a photosensitizer solution to the cornea, and using UV light to cross-link collagen and reinforce tissues that display viscoelastic creep. CXL could have shorter recovery times and better outcomes if patients' epithelial layers are left intact, but this barrier prevents sufficient and uniform delivery of photosensitizer to the inner, diseased layer (the stroma). As a means of attaining sufficient mass flux and uniform delivery of cross-linking agent, our group has developed technology to embed solid, monodisperse spheres (10-50 um) composed of photosensitizer (Eosin Y) in sub-epithelial layers. A vibrating orifice aerosol generator is used to discharge drug solution into a temperature/humidity controlled column to synthesize glassy microparticles made of Eosin Y. Highly controlled pneumatic devices have been developed to accelerate microparticles without emitting damaging, pressurized gas. It has been shown that not only can this be a viable therapy, but also that there exist novel, nonlinear impact mechanics when particles embed in fibrous biomatter at high strain rates. |
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