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 J11: Morphogenesis IFocus Live
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Sponsoring Units: DBIO Chair: Zi Chen, Dartmouth College; Andrej Kosmrlj, Princeton University |
Tuesday, March 16, 2021 3:00PM - 3:36PM Live |
J11.00001: Physical aspects of cell and tissue elongation Invited Speaker: Samhita Banavar Shaping cells and tissues requires a tight spatiotemporal control of several physical quantities during morphogenesis. Actively-generated stresses as well as material properties and growth can all be tuned in space and time and contribute to building functional structures, with multiple molecular processes and feedbacks enabling the spatiotemporal regulation of these physical fields. In this talk, I will focus on cell and tissue elongation and highlight a common physical mechanism of elongating individual wall cells and animal embryonic tissues. I will present the results of theoretical studies of the dynamics of growth of mating projections in budding yeast cells and also of body axis elongation in zebrafish embryos, using coarse grained approaches and basic physical principles. Our results, which are in agreement with experimental observations, show that the existence of spatially and temporally regulated fluid-to-solid transitions in the structures being sculpted is essential for both cell and tissue elongation. |
Tuesday, March 16, 2021 3:36PM - 3:48PM Live |
J11.00002: Hydraulic and electric control of cell spheroids Charlie Duclut, Jacques Roger Prost, Frank Jülicher In addition to generating forces and reacting to mechanical cues, tissues are capable to actively pump fluid and create electric current. In this talk, we will discuss how a hydraulic or electrical perturbation, imposed for instance by a drain of micrometric diameter, can be used to perturb tissue growth. We address this issue in a continuum description of a spherical cell assembly that includes the mechanical, electrical and hydraulic properties of the tissue. This approach allows us to discuss and quantify the effect of electrohydraulic perturbations on the long-time states of the tissue. We highlight that a sufficiently strong external flow or electric current can drive a proliferating spheroid to decay. We propose that this could have applications in medicine. |
Tuesday, March 16, 2021 3:48PM - 4:00PM Live |
J11.00003: A reproducible human stem cell system reveals neural tube morphogenesis Eyal Karzbrun, Aimal Khankhel, Heitor Megale, Boris I Shraiman, Sebastian Streichan Neural tube folding is one of the earliest morphogenetic events in the human embryo, with defects affecting 1:1000 pregnancies a year. Years of studies in animal models, revealed species dependent mechanisms for neural tube formation, yet the origin of forces which drives tissue folding remains under debate. Recent advances in 3D stem-cell cultures [Organoids] raised a promise to study developmental biology in a human genetic context. However, the large variability and lack of predictability in organoid systems, severely limits their potential applications. Here, we developed a highly reproducible three-dimensional human stem-cell culture, essentially solving the organoid variability problem. Remarkably, our system exhibits folding morphogenesis which is highly similar to neural tube formation. We perform a quantitative morphometric analysis, and discover that folding morphogenesis is driven by a combination of cell contractility and active tissue wetting. These findings have strong implications to our understanding of neural tube development in humans. In the future, our platform can be expanded to study morphogenesis of additional organs, from the lung to the heart. |
Tuesday, March 16, 2021 4:00PM - 4:12PM Live |
J11.00004: Integrating space and time in patterning of gene expression in embryogenesis via a synthetic approach Huy Tran, Gonçalo Fernandes, Mathieu Coppey, Nathalie Dostatni, Aleksandra Walczak During development, reproducible cell identity is established through the expression of specific genes at the correct time and correct location in space in all individuals. It remains unclear how genes extract and combine both positional and temporal information from different transcription factor (TF) profiles along embryo or tissue axes. Here, we showcase the classic hunchback gene, with focus on 3 of its main TFs during Drosophila early embryogenesis: Bicoid, Zelda and Hunchback proteins. We constructed a series of synthetic ms2 reporters, where the numbers of binding sites for each TF are varied systematically. Using live-imaging of transcription dynamics by these synthetic reporters and modeling tools, we show that Bicoid and Zelda act as sources of positional information for gene expression. Notably, they are found to regulate in synergy the same steps in transcription initiation. Meanwhile, the Hunchback protein, which constitutes a feedback on the hunchback gene expression, targets the downstream steps of the transcription process, independent of Bicoid and Zelda. With the regulatory mechanisms of individual TFs identified, we hope to shed light on when and how robust cell identity can be established from the dynamical gap genes patterns |
Tuesday, March 16, 2021 4:12PM - 4:24PM Live |
J11.00005: Light controlled cell-fates in embryonic development Anand Singh, Ping Wu, Eric F. Wieschaus, Jared Toettcher, Thomas Gregor During embryonic development, cellular fates are tightly regulated in space and time. Transcription factors (TFs) play a critical role in cell fate determination. However, complex regulatory codes and mechanisms make it challenging to interpret a direct role of TF inputs in gene activity. To overcome these challenges, we have combined light perturbation of TF input, real-time gene output measurements, and Drosophila genetics to build synthetic spatial and temporal gene activity patterns in living fly embryos. In particular, we have built a light delivery platform that allows for flexible light patterns to instruct light-sensitive TFs in space and time. Upon light illumination, TFs translocate to the cytosolic compartment and allow for modulation of nuclear TF concentration and thus downstream gene activity patterns. We are developing a quantitative approach to modulate TF’s input concentration and record transcriptional gene output in real-time to bring a new dimension to the study of transcriptional dynamics in a developing embryo. |
Tuesday, March 16, 2021 4:24PM - 4:36PM Live |
J11.00006: From super-resolution imaging to theory: cadherin clustering drives asymmetric glassy dynamics during vertebrate embryo elongation Abdul Malmi Kakkada, Robert Huebner, Sena Sarikaya, Shinuo Weng, Dave Thirumalai, John Wallingford Convergent extension is a mode of collective cell movement driven by cell intercalation, underlying tissue elongation in nematodes, arthropods and vertebrates. Defective convergent extension is implicated in catastrophic neural tube birth defects. By combining theoretical modeling and analysis of super-resolution imaging of Xenopus laevis embryos, we show that intracellular C-cadherin (Cdh3) cis-clustering regulates the local vertex viscoelasticity at subcellular length scales. We uncover that spatially heterogenous cadherin clustering drives asymmetric vertex dynamics in convergent extension, exhibiting features of glassy dynamics observed in non-equilibrium materials such as colloidal glasses and gels. Even as defective clustering of C-cadherin can facilitate tissue coherence in vivo, we discover that clustering of C-cadherin is crucial in the more mechanically challenging context of convergent extension. |
Tuesday, March 16, 2021 4:36PM - 4:48PM Live |
J11.00007: Physics-Informed Deep Learning for Characterizing Perturbed Cell Growth Henry Cavanagh, Robert G Endres, Rob Lind, Andreas Mosbach, Gabriel Scalliet The morphodynamical analysis of cells can be a powerful and cost-effective way of understanding the phenotypic effects of perturbations, but current techniques often only work for stationary cell morphology. Here, we introduce a novel framework that extends behavior analysis to nonstationary morphodynamics during early stage growth of the soybean rust pathogen, P. pachyrhizi. At its core, our approach learns the 2-dimensional feature space of cell shape using variational autoencoders from deep learning, and subsequently models how populations of cells develop over this space using two simple differential equations, each capturing complementary aspects of the dynamics, and with parameters depending on the perturbations. We compared two models: a Fokker-Planck model to describe the diffusive development on a Waddington-type energy landscape, providing a global perspective on the dynamics; and a cell-mechanical model describing local growth as a persistent random walk. Informative perturbation-dependent parameters are found by fitting simulations to the shape space embeddings, representing a powerful tool for linking machine-learning and biophysical modelling. |
Tuesday, March 16, 2021 4:48PM - 5:00PM Live |
J11.00008: Modelling the dynamics of shape change in a patterned viscoelastic sheet Abhijeet Krishna, Carl D Modes There is a wide-scale interest in the study of material sheets that change their 3D shape on being stimulated. Examples include liquid crystal elastomers that deform upon heat or light variations or monolayer epithelia that deform during the development of an organism. Previous studies have dealt with the equilibrium geometry and energy description of shape changes within the framework of elasticity theory. In our study, we take a different direction by introducing viscoelasticity and studying the dynamics analytically and in spring-dashpot lattice simulations. As an example, we study a frustrated flat sheet that relaxes into semi-spherical configuration. We trace the dynamics of our simulations and show that the geometry of the final shape is independent of the viscoelastic parameters. Our simulations reveal the emergence of a characteristic time-scale before appearance of curvature, reminiscent of the classical buckling transition, where beyond a critical thickness, the sheet stays flat in order to avoid high bending energy. Finally, we discuss the dependence of this time-scale on the viscoelastic coefficients and show that adding spatial variability in the viscoelastic parameters leads to disappearance in this delay in appearance of curvature while retaining the final shape. |
Tuesday, March 16, 2021 5:00PM - 5:12PM Live |
J11.00009: The finch beak: growth, form and function Salem AlMosleh, Gary Choi, Arkhat Abzhanov, L. Mahadevan Darwin's finches are a classic example of adaptive radiation, exemplified by their adaptive and functional beak morphologies. Using 3D scans of skulls in this group, we perform an evolutionary morphometric analysis of the three-dimensional beak shapes and find that they can be fit by a simple functional form: the transverse sections of the beaks are parabolas with a curvature that decreases linearly with distance away from the tip of the beak. Guided by our morphometric analysis of finch beaks and earlier observations of the development of the zebra finch beak, we propose a minimal cellular and tissue level mechanism for beak morphogenesis that takes the form of a local geometric growth law. We show that this variant of curvature-driven flow captures the range of observed shapes of the finch beak in terms of two geometric parameters set by the size and shape of the developing beak bud. Finally we consider the role of beak orientation, along with its size and shape as determinants of its mechanical performance quantified in terms of the mechanical advantage of the beak treated as an elementary machine, and consider this in the context of the variable diets of finches. |
Tuesday, March 16, 2021 5:12PM - 5:24PM Live |
J11.00010: Reconstruct cellular dynamics from single cell data Weikang Wang, Dante Poe, Ke Ni, Jianhua Xing Recent advances of single cell techniques catalyzed quantitative studies on the dynamics of cell phenotypic transitions (CPT) emerging as a new field. However, fixed cell-based approaches have fundamental limits on revealing temporal information, and fluorescence-based live cell imaging approaches are technically challenging for multiplex long-term imaging. To tackle the challenges, we developed an integrated experimental/computational platform for reconstructing single cell phenotypic transition dynamics. Experimentally, we developed a live-cell imaging platform to record the phenotypic transition path of A549 VIM-RFP reporter cell line and unveil parallel paths of epithelial-to-mesenchymal transition (EMT). Computationally, we modified a finite temperature string method to reconstruct the reaction coordinate from the paths, and reconstruct a corresponding quasi-potential, which reveals that the EMT process resembles a barrier-less relaxation process. Our work demonstrates the necessity of extracting dynamical information of phenotypic transitions and the existence of a unified theoretical framework describing transition and relaxation dynamics in systems with and without detailed balance. |
Tuesday, March 16, 2021 5:24PM - 5:36PM Live |
J11.00011: In vivo measurement of tissue mechanical properties in Drosophila embryos An Pham, Chonglin Guan, Daniel P. Kiehart, Christoph F. Schmidt Material properties determine how tissues respond to forces during embryo morphogenesis. The regulation of both material properties and force generation are key to directing the complex tissue movements required in embryonic development. Quantitative measurements of tissue material properties are challenging because it is usually difficult to access tissues inside a living embryo for mechanical probing. Here, we introduce two experimental approaches, magnetic tweezers and glass microneedles, to probe tissue mechanical properties in Drosophila embryos peeled out of their vitelline egg shells. We image tissue deformations during the process of dorsal closure in a microscope when we exert mechanical stresses by either a magnetic bead or a pair of calibrated glass microneedles. These measurements allow us to calculate viscoelastic material response properties of the tissue probed. |
Tuesday, March 16, 2021 5:36PM - 5:48PM Live |
J11.00012: Morphing of growing sheets via active contractions of muscle cells Anvitha Sudhakar, Andrej Kosmrlj Morphological shape transformations in biological systems often arise from patterned biochemical processes, which can produce mechanical forces either actively via molecular motors or passively via differential growth of connected tissues. Both the active contractions and the growth mismatch between tissues produce internal stresses, which are released by shape transformations and mechanical instabilities. Such processes play important roles for shaping of brain, guts, lungs and other organs in developing organisms. Inspired by these biological systems, we investigate how growing epithelial sheets can be folded into complex structures by active contractions of neighbouring smooth muscle cells. To capture large deformations of soft tissues we developed a theoretical and computational framework based on the finite strain theory, where the total deformation gradient tensor was decomposed into one part due to growth/active contractions and another part due to elastic deformation. This framework was then used to predict folding of growing epithelium in response to patterned contractions of smooth muscle cells. These results help illuminate what kind of processes are needed to generate the complex architectures found within tissues in developing organisms. |
Tuesday, March 16, 2021 5:48PM - 6:00PM Live |
J11.00013: Dimensionality-Reduction in the Drosophila Wing as Revealed by Landmark-Free Measurements of Phenotype Vasyl Alba, James E Carthew, Madhav Mani, Richard Carthew Organismal phenotypes emerge from a complex set of genotypic interactions. While technological advances in sequencing provide a quantitative description of an organism’s genotype, characterization of an organism’s physical phenotype lags far behind. Here, we relate genotype to the complex and multi-dimensional phenotype of an anatomical structure using the Drosophila wing as a model system. We develop a mathematical approach that enables a robust description of biologically salient phenotypic variation. Analysing natural phenotypic variation, and variation generated by weak perturbations in genetic and environmental conditions during development, we observe a highly constrained set of wing phenotypes. In a striking example of dimensionality reduction, the nature of varieties produced by the Drosophila developmental program is constrained to a single integrated mode of variation in the wing. Our strategy demonstrates the emergent simplicity manifest in the genotype-to-phenotype map in the Drosophila wing and may represent a general approach for interrogating a variety of genotype-phenotype relationships. |
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