Bulletin of the American Physical Society
APS March Meeting 2020
Volume 65, Number 1
Monday–Friday, March 2–6, 2020; Denver, Colorado
Session G26: Morphogenesis, Tissues, and Cancer |
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Sponsoring Units: DBIO Chair: Zi Chen, Dartmouth Coll Room: 403 |
Tuesday, March 3, 2020 11:15AM - 11:27AM |
G26.00001: Investigation into the dynamics of lipid membrane remodeling Abhimanyu Sharma, Henry Nguyen, Nathaniel Talledge, John McCullough, Frank Moss III, Janet Iwasa, Michael Vershinin, Wesley Sundquist, Adam Frost Lipid membranes play a key role in biology, enclosing entire living cells, as well as intracellular compartments. Cellular processes such as endocytosis, virus budding, and cytokinesis involve changes in membrane shape and connectivity. Membrane remodeling is essential, common, and tightly regulated. A variety of pathways, including the endosomal sorting complexes required for transport (ESCRT) machinery are involved in locally changing membrane curvature (both invagination and evagination), tabulation, and scission. However, the mechanics of many of these remodeling events are still poorly understood. We have used an in vitro GUV system, and investigated the details of membrane reshaping under local mechanical load and in several ESCRT protein backgrounds. We will discuss our results, which demonstrate how protein-based regulation can help remodel bilayer membranes. |
Tuesday, March 3, 2020 11:27AM - 11:39AM |
G26.00002: Investigating cell shape changes during organogenesis using a 3D vertex model Paula Sanematsu, Gonca Erdemci-Tandogan, Matthias Merkel, Jeffrey D. Amack, M. Lisa Manning Left-right (LR) asymmetry present in internal organs of vertebrates initiates during embryonic development with observable changes to individual cell shapes which are vital to the creation of functional organs. However, the mechanisms that drive cell shape changes remain poorly understood. Kupffer’s vesicle (KV) is a transient organ in the Zebrafish embryo that acts as the LR organizer. As the KV moves through the surrounding tissue during development, KV cells change shape along the anterior-posterior (AP) axis, a necessary process for subsequent LR asymmetry[1]. Erdemci-Tandogan et al.[2] used a 2D vertex model and experimental data to show that surrounding tissue rheology and KV cell motility could drive KV cell shape changes. Since the KV is inherently 3D, and that 2D and 3D drag forces can be very different, we extend that work by studying drag forces on the KV in a 3D model. We show that cell shape changes along the AP axis do occur in 3D due to drag forces. By implementing particle-image-velocimetry (PIV) analysis, we quantitatively compare simulation and experimental data of the flow of surrounding cells past the KV as it develops. |
Tuesday, March 3, 2020 11:39AM - 11:51AM |
G26.00003: Patterning-Mechanics Feedback Mechanism to Understand Axis Extension during Morphogenesis Samira Anbari, Javier Buceta Fernandez Within the topic of morphogenesis, tissue elongation is a necessary process in all metazoans to shape their body plans which is not fully understood. For example, in the particular case of the limb, it has been shown that tissue elongation cannot be explained by either a localized proliferation of cells or their oriented divisions and, surprisingly, the tissue elongates perpendicular to the direction along which cell grow. Here we propose a mechanism of tissue elongation that couples the mechanical properties of cells with the concept of positional information to modulate the former in a location-dependent manner. To illustrate our proposal, we use morphogen gradient thresholds as well as Turing patterning system as the mean used by cells to “know” their relative positions within a primordium. Our numerical simulations are based on the vertex model system and we show that if the cell-cell adhesion is modulated as a function of the location of cells within a primordium, an auto-catalytic cell intercalation process develops and the tissue elongates. Moreover, our results reveal that cells grow perpendicular to the elongation direction as experimentally reported. Altogether, our results shed light on the tissue elongation problem and pave the way to better understand morphogenesis. |
Tuesday, March 3, 2020 11:51AM - 12:03PM |
G26.00004: Morphogenesis and fractal dimension of bacterial pellicles Boyang Qin, Ned Wingreen, Bonnie Bassler, Howard A Stone Bacteria cells can self-organize into structured communities at phase boundaries, known as biofilms. At liquid-liquid and liquid-air interfaces, these soft, living materials of cells and extracellular polysaccharides – called pellicles – confer survival advantages and protection against environmental insults to the community. These benefits are not attainable by individual planktonic cells. The mechanics driving pellicle formation and morphology are not understood. Here, using a home-made adaptive stereoscope instrument and fluorescent microscopy, we identify a series of mechanical and architectural transitions in Vibrio cholerae pellicles at a liquid-oil interface. There are three distinct stages: emergence of founding colonies, onset of primary and secondary wrinkling instabilities, and a fractal-order increase in complexity. We show that although cells in a pellicle share a habitat, founder colonies remain monoclonal, hence the community maintains spatial and genetic heterogeneity. |
Tuesday, March 3, 2020 12:03PM - 12:15PM |
G26.00005: Learning about human development from clinical IVF data Brian Leahy, Helen Yang, Won-dong Jang, Dalit Ben-Yosef, Vinothan Manoharan, Daniel Needleman The early human embryo is the physicist's dream for studying development. Between fertilization and implantation in the uterus, mammalian embryos undergo a global reorganization (compaction) followed by a symmetry-breaking differentiation (blastocyst formation), with no external direction from the mother. But for ethical reasons, we cannot do experiments with human embryos. So how can we understand human development without experiments? Here, we examine tens of thousands of videos of human embryos recorded during routine clinical IVF procedures. We use those videos to explore the natural variability in mammalian preimplantation embryo development, and we leverage this variability to identify critical factors in early development. |
Tuesday, March 3, 2020 12:15PM - 12:27PM |
G26.00006: Emergence of helical growth and morphogenesis in fungal cells from cell wall dynamics Shankar Lalitha Sridhar, Guillaume Lostec, Joseph K.E. Ortega, Franck J. Vernerey Walled cells such as plants, algae and fungi achieve expansive growth using turgor pressure that helps mediate irreversible wall deformation and regulates their shape and volume. The architecture of the cell wall plays a crucial role in this process where a network of microfibrils and tethers (complex polysaccharides and proteins) dynamically mediate the network topology via continuous detachment and reattachment events. The growth of Phycomyces blakesleeanus, a wiry single-celled sporangiophore that typically grows longitudinally, is particularly intriguing as it also rotates (clockwise from top) indicating helical growth. There is no apparent functional purpose for this rotation which has led to speculation that it is a direct consequence of wall architecture, and specifically a microfibril re-orientation mechanism. Interestingly, in piloboloid mutants longitudinal growth is combined with radial growth to produce a rotation inversion, i.e. anti-clockwise rotation. In this talk, we will present a novel approach based in statistical mechanics to model the organization and dynamics of microfibrils and tethers in the cell wall of to help explain this phenomenon. |
Tuesday, March 3, 2020 12:27PM - 12:39PM |
G26.00007: Understanding cell contact constriction in epithelial morphogenesis through data driven reverse-time inference Nicolas Lenner, Deqing Kong, Stephan Eule, Jörg Großhans, Fred Wolf Tissue elongation via convergent extension mediated by cell intercalation is a frequent mechanism in the development of metazoans. During Drosophila germband extension cell intercalation is achieved by acto-myosin driven junction shrinkage of neighboring cells, its resolution into a vertex of four neighboring cells, and subsequent junction formation in orthogonal direction. Despite tremendous progress in the understanding of the molecular underpinnings involved in this process called a T1 transition, a quantitatively tested mechanism that predicts the dynamics of individual cell-junctions is still not available. We here show how our mathematically novel approach of reverse time ensemble inference allows to infer the process of junction shrinkage in reverse time, starting from the endpoint of the dynamic, i.e. the 4-vertex. We apply our inference scheme to ~1000 T1 transitions and systematically rule out model classes of increasing complexity using all accessible ensemble statistics. We find visco-elastic like dynamics, infer the onset of each individual junction collapse and link the inferred junctional dynamics to the simultaneously recorded myosin dynamics. |
Tuesday, March 3, 2020 12:39PM - 12:51PM |
G26.00008: Experiments and modeling of “irreversible” brain torsion in early chick embryos Zi Chen, Hao Zhang, Guangchao Wan, Wei Zeng, Hannah Grover, Shicheng Huang The rightward torsion of the chick embryonic brain tube is one of the earliest organ-level left-right asymmetry developmental events, often associated with birth defects such as situs inversus, but the biomechanics of this process remains incompletely understood. Previous works showed that vitelline membrane (VM) exerts a force on the brain that drives the torsion, and surface tension (ST) can replace the mechanical role of VM. However, our experiments showed when ST was removed the torsion does not fully reverse suggesting other overlooked mechanical factors. Here, we use a combination of experiments and modeling to reveal that the deformation during the early brain torsion can be path and stage dependent. With optical coherence tomography imaging, we tracked the twisting and untwisting in a step-wise manner. A computational model is employed to help interpret the findings, in particular the path-dependent, "irreversible" shape evolution. Results show that the body forces such as gravity and buoyancy also play an important role during this left-right asymmetric morphogenesis process, thus revealing the hidden mechanical factors in the normal and abnormal development of early embryos. |
Tuesday, March 3, 2020 12:51PM - 1:03PM |
G26.00009: Dynamics of a single cell fate decision Simon Freedman, Kristin Johnson, Carole LaBonne, Madhav Mani As an animal develops from a fertilized egg into a complex multicellular organism, its cells change from being pluripotent to lineage restricted. These state changes are often driven by morphogens, molecules that launch signalling cascades that affect DNA transcription and modify a cell’s protein makeup. While morphogens and cell fates have been extensively identified, the process through which a morphogen changes a cell’s fate is not well understood. To elucidate these dynamics, we performed bulk RNA sequencing at multiple time points during a single cell fate decision in which pluripotent Xenopus laevis (African frog) cells differentiate to one of two fates: neural progenitor and epidermis. We found that the geometric structure of both transitions include linear temporal trends that correspond with development toward a neural fate, and that epidermal fated cells exhibit a second, non-linear temporal trend that corresponds with BMP activation. Our analyses enabled us to predict a point-of-no-return for the epidermal fate, which we experimentally verified. Our work highlights the importance of examining intermediate developmental times to discern fate specification, and sheds light on distinguishing the internal and external forces that drive embryonic development. |
Tuesday, March 3, 2020 1:03PM - 1:15PM |
G26.00010: Binary establishment and maintenance of discrete cell fates in development Jiaxi Zhao, Jacques Bothma, Matthew Norstad, Hernan G. Garcia During embryonic development, cells must ultimately adopt discrete fates. Positive autoregulation has been proposed as a general mechanism for establishing and maintaining these discrete cell-fate decisions. Here, we quantitatively dissect the role of autoregulation and bistability in establishing binary cellular fates in the fruit fly Drosophila melanogaster. Specifically, we apply recently developed single-cell live imaging techniques to quantify transcriptional and protein dynamics of the Drosophila pair-rule gene fushi tarazu as cells decide whether to commit to the expression of the gene. |
Tuesday, March 3, 2020 1:15PM - 1:27PM |
G26.00011: A variational principle for power dissipation in low frequency conduction in biological tissues. Francisco Solis, Vikram Jadhao Propagation of low-frequency electrical signals in biological tissues appears naturally in neural and cardiac physiological systems. These signals can also be externally applied to tissues as part of experimental probes or therapeutic tools. Models for propagation of these signals usually consider tissues as purely conductive materials. In large systems such as whole bodies or organs, these models consider the systems as composed of finite domains of homogeneous regions with distinct conductivities. The electric fields in these model systems exhibiting piecewise-uniform conductivity obey equations similar to those of electrostatics in polarizable media, but with boundary conditions set by current conservation. In this presentation we show that the electric fields can be obtained via a variational principle based on the minimization of dissipated power. In addition to providing a conceptual framework to the problem, this principle allows the construction of approximate solutions. It can also be used to establish bounds on the spectrum of the integral and differential operators that appear naturally in these problems. |
Tuesday, March 3, 2020 1:27PM - 1:39PM |
G26.00012: A biophysical model uncovers the size distribution of migrating cell clusters across cancer types Federico Bocci, Mohit Kumar Jolly, Jose N Onuchic Migration from the primary tumor is a crucial step in the metastatic cascade. Cells with various degrees of adhesion and motility migrate into the bloodstream as single circulating tumor cells (CTCs) or multi-cellular CTC clusters. The frequency and size distributions of these clusters have been recently measured, but the underlying mechanisms enabling these different modes of migration remain poorly understood. We present a biophysical model that couples intra-tumoral heterogeneity enabled by the epithelial-mesenchymal transition (EMT) with cell migration to explain the modes of individual and collective cancer cell migration. This reduced physical model undergoes a transition from individual migration to collective cell migration and robustly recapitulates CTC cluster fractions and size distributions observed experimentally across several cancer types, thus suggesting the existence of common features in the mechanisms underlying cancer cell migration. Overall, this biophysical model provides a platform to continue to bridge the gap between the molecular and biophysical regulation of cancer cell migration, and highlights that a complete EMT might not be required for metastasis. |
Tuesday, March 3, 2020 1:39PM - 1:51PM |
G26.00013: Spatial Distribution of Immune Cells in Tumors Juliana C. Wortman, Ting-Fang He, Shawn Solomon, Robert Zhang, Anthony Rosario, Roger Wang, Travis Y. Tu, Daniel Schmolze, Yuan Yuan, Susan E. Yost, Xuefei Li, Herbert Levine, Gurinder Atwal, Peter P. Lee, Clare Yu The goal of immunotherapy is to enhance the ability of the immune system to kill cancer cells. Immunotherapy is more effective and, in general, the prognosis is better, when more immune cells infiltrate the tumor. We describe various techniques we have developed to explore the question of whether the spatial distribution rather than just the density of immune cells in the tumor is important in forecasting whether cancer recurs. We apply our approach to immune cells in images of tumor tissue taken from (triple negative) breast cancer patients. We find that there is a distinct difference in the spatial distribution of immune cells between good clinical outcome (no recurrence of cancer within at least 5 years of diagnosis) and poor clinical outcome (recurrence within 3 years of diagnosis). |
Tuesday, March 3, 2020 1:51PM - 2:03PM |
G26.00014: Computationally tractable mechanistic model of inhomogeneous -- anisotropic drug diffusion and tumor ablation Erdi Kara, Aminur Rahman, Eugenio Aulisa, Souparno Ghosh In this work, we study the effect of drug distribution on tumor cell death when the drug is internally injected in the tumorous tissue. We derive a full 3-dimensional inhomogeneous – anisotropic diffusion model. To capture the anisotropic nature of the diffusion process in the model, we use an MRI data of a 35-year old patient diagnosed |
Tuesday, March 3, 2020 2:03PM - 2:15PM |
G26.00015: A possible role for epigenetic feedback regulation in the dynamics of the epithelial–mesenchymal transition (EMT) Wen Jia, Abhijeet Deshmukh, Sendurai A Mani, Mohit Kumar Jolly, Herbert Levine Epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis and drug resistance, and involves epigenetic remodeling. However, how epigenetic changes affecting the dynamical traits such as plasticity or memory are not fully understood. Here, we analyzed the effects of epigenetic feedback on EMT through integrating this feedback on various aspects of the miR-200/ZEB loop – a core circuit regulating EMT. Epigenetic feedback on self-activation of ZEB has minor effects in population distribution and transition times, but epigenetic feedback on the inhibition of miR-200 by ZEB can largely stabilize the mesenchymal state, thus making the process irreversible. Follow-up preliminary experiments show that when EMT is induced in epithelial cells , a certain percentage of cells can stay in mesenchymal state after the inducing signal is removed. This percentage depends on the extent of induction of EMT, thus well recapitulating our model-based predictions. |
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