scholarly journals 3D viscoelastic drag forces drive changes to cell shapes during organogenesis in the zebrafish embryo

2021 ◽  
Author(s):  
Paula C. Sanematsu ◽  
Gonca Erdemci-Tandogan ◽  
Himani Patel ◽  
Emma M. Retzlaff ◽  
Jeffrey D. Amack ◽  
...  
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
New Physics ◽  
Tissue Mechanics ◽  
List Type ◽  
Drag Forces ◽  
Velocity Gradients ◽  
Cell Shapes ◽  
Cell Shape Changes ◽  
Shape Changes

AbstractThe left-right organizer in zebrafish embryos, Kupffer’s Vesicle (KV), is a simple organ that undergoes programmed asymmetric cell shape changes that are necessary to establish the left-right axis of the embryo. We use simulations and experiments to investigate whether 3D mechanical drag forces generated by the posteriorly-directed motion of the KV through the tailbud tissue are sufficient to drive such shape changes. We develop a fully 3D vertex-like (Voronoi) model for the tissue architecture, and demonstrate that the tissue can generate drag forces and drive cell shape changes. Furthermore, we find that tailbud tissue presents a shear-thinning, viscoelastic behavior consistent with those observed in published experiments. We then perform live imaging experiments and particle image velocimetry analysis to quantify the precise tissue velocity gradients around KV as a function of developmental time. We observe robust velocity gradients around the KV, indicating that mechanical drag forces must be exerted on the KV by the tailbud tissue. We demonstrate that experimentally observed velocity fields are consistent with the viscoelastic response seen in simulations. This work also suggests that 3D viscoelastic drag forces could be a generic mechanism for cell shape change in other biological processes.Highlightsnew physics-based simulation method allows study of dynamic tissue structures in 3Dmovement of an organ through tissue generates viscoelastic drag forces on the organthese drag forces can generate precisely the cell shape changes seen in experimentPIV analysis of experimental data matches simulations and probes tissue mechanicsGraphical abstract

scholarly journals Tissue flow induces cell shape changes during organogenesis

2018 ◽  
Author(s):  
Gonca Erdemci-Tandogan ◽  
Madeline J. Clark ◽  
Jeffrey D. Amack ◽  
M. Lisa Manning
Keyword(s):  
Cell Shape ◽  
Surrounding Tissue ◽  
Model Parameters ◽  
Drag Forces ◽  
Dynamic Forces ◽  
Cell Shapes ◽  
Specific Shape ◽  
Cell Shape Changes ◽  
Shape Changes ◽  
Anterior Posterior

In embryonic development, cell shape changes are essential for building functional organs, but in many cases the mechanisms that precisely regulate these changes remain unknown. We propose that fluid-like drag forces generated by the motion of an organ through surrounding tissue could generate changes to its structure that are important for its function. To test this hypothesis, we study the zebrafish left-right organizer, Kupffer’s vesicle (KV), using experiments and mathematical modeling. During development, monociliated cells that comprise the KV undergo region-specific shape changes along the anterior-posterior axis that are critical for KV function: anterior cells become long and thin, while posterior cells become short and squat. Here, we develop a mathematical vertex-like model for cell shapes, which incorporates both tissue rheology and cell motility, and constrain the model parameters using previously published rheological data for the zebrafish tailbud [Serwane et al.] as well as our own measurements of the KV speed. We find that drag forces due to dynamics of cells surrounding the KV could be sufficient to drive KV cell shape changes during KV development. More broadly, these results suggest that cell shape changes could be driven by dynamic forces not typically considered in models or experiments.

A dominant inhibitory version of the small GTP-binding protein Rac disrupts cytoskeletal structures and inhibits developmental cell shape changes in Drosophila

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 903-914 ◽  
Author(s):  
N. Harden ◽  
H.Y. Loh ◽  
W. Chia ◽  
L. Lim
Keyword(s):  
Epidermal Cell ◽  
Cell Shape ◽  
Shape Change ◽  
Yeast Cells ◽  
Cell Shape Change ◽  
Gtp Binding ◽  
Wide Range ◽  
Cell Shape Changes ◽  
Germband Retraction ◽  
Shape Changes

The Rho subfamily of Ras-related small GTP-binding proteins is involved in regulation of the cytoskeleton. The cytoskeletal changes induced by two members of this subfamily, Rho and Rac, in response to growth factor stimulation, have dramatic effects on cell morphology. We are interested in using Drosophila as a system for studying how such effects participate in development. We have identified two Drosophila genes, DRacA and DRacB, encoding proteins with homology to mammalian Rac1 and Rac2. We have made transgenic flies bearing dominant inhibitory (N17DRacA), and wild-type versions of the DRacA cDNA under control of an Hsp70 promoter. Expression of the N17DRacA transgene during embryonic development causes a high frequency of defects in dorsal closure which are due to disruption of cell shape changes in the lateral epidermis. Embryonic expression of N17DRacA also affects germband retraction and head involution. The epidermal cell shape defects caused by expression of N17DRacA are accompanied by disruption of a localized accumulation of actin and myosin thought to be driving epidermal cell shape change. Thus the Rho subfamily may be generating localized changes in the cytoskeleton during Drosophila development in a similar fashion to that seen in mammalian and yeast cells. The Rho subfamily is likely to be participating in a wide range of developmental processes in Drosophila through its regulation of the cytoskeleton.

Collagenase secretion accompanying changes in cell shape occurs only in the presence of a biologically active cytokine

1989 ◽  
Vol 92 (3) ◽  
pp. 473-485
Author(s):  
I. Kuter ◽  
B. Johnson-Wint ◽  
N. Beaupre ◽  
J. Gross
Keyword(s):  
Cell Cultures ◽  
Cell Shape ◽  
Cell Function ◽  
Shape Change ◽  
Biologically Active ◽  
Target Cells ◽  
Mixed Cell ◽  
Cell Shape Change ◽  
Cell Shape Changes ◽  
Shape Changes

We have investigated the relationship between collagenase production, cell shape and stimulatory factors in cell culture. In a homogeneous culture of primary rabbit corneal stromal cells, shape change induced by a variety of agents was not effective in stimulating collagenase secretion. Only in the presence of a biologically active cytokine or phorbol myristate acetate was a correlation seen between changes in cell shape (induced by a second agent) and collagenase secretion by these primary cells. Cell shape changes were not, however, necessary for collagenase secretion, since certain concentrations of endotoxin or lactalbumin hydrolysate effected secretion of the enzyme in the absence of morphological changes. With passaged cells or mixed cell cultures, where cell shape change did correlate with collagenase secretion without the addition of an exogenous agent, the production of an effective cytokine (autocrine or paracrine) was demonstrated. Thus cell shape change seems to be neither universally necessary nor sufficient for the stimulation of collagenase secretion. It is proposed that the function of cytokines may be more immediately related to gene expression in this system than is change in the shape of the cell. The hypothesis is presented that cell shape changes may render the target cells receptive to cytokines, perhaps by replacing the need for a natural cytokine cofactor. It is also demonstrated here that the use of passaged cells, mixed cell cultures containing endogenous cytokine-secreting cells or tissue culture additives can profoundly affect the interpretation of the effect of various agents on collagenase secretion, and may lead to observations that are not directly relevant to cell function in vivo.

scholarly journals Mathematical modelling in cell migration: tackling biochemistry in changing geometries

2020 ◽  
Vol 48 (2) ◽  
pp. 419-428
Author(s):  
Björn Stinner ◽  
Till Bretschneider
Keyword(s):  
Cell Migration ◽  
Molecular Motors ◽  
Cell Shape ◽  
Reaction Diffusion ◽  
Level Line ◽  
External Signal ◽  
Interface Capturing ◽  
Cell Shapes ◽  
Cell Shape Changes ◽  
Shape Changes

Directed cell migration poses a rich set of theoretical challenges. Broadly, these are concerned with (1) how cells sense external signal gradients and adapt; (2) how actin polymerisation is localised to drive the leading cell edge and Myosin-II molecular motors retract the cell rear; and (3) how the combined action of cellular forces and cell adhesion results in cell shape changes and net migration. Reaction–diffusion models for biological pattern formation going back to Turing have long been used to explain generic principles of gradient sensing and cell polarisation in simple, static geometries like a circle. In this minireview, we focus on recent research which aims at coupling the biochemistry with cellular mechanics and modelling cell shape changes. In particular, we want to contrast two principal modelling approaches: (1) interface tracking where the cell membrane, interfacing cell interior and exterior, is explicitly represented by a set of moving points in 2D or 3D space and (2) interface capturing. In interface capturing, the membrane is implicitly modelled analogously to a level line in a hilly landscape whose topology changes according to forces acting on the membrane. With the increased availability of high-quality 3D microscopy data of complex cell shapes, such methods will become increasingly important in data-driven, image-based modelling to better understand the mechanochemistry underpinning cell motion.

scholarly journals Cellular structure image classification with small targeted training samples

2019 ◽  
Author(s):  
Dali Wang ◽  
Zheng Lu ◽  
Yichi Xu ◽  
Zi Wang ◽  
Chengcheng Li ◽  
...  
Keyword(s):  
Deep Learning ◽  
Image Classification ◽  
Cell Shape ◽  
Time Lapse ◽  
Training Dataset ◽  
Generative Adversarial Networks ◽  
Training Samples ◽  
Cell Shapes ◽  
Cell Shape Changes ◽  
Shape Changes

AbstractMotivationCell shapes provide crucial biology information on complex tissues. Different cell types often have distinct cell shapes, and collective shape changes usually indicate morphogenetic events and mechanisms. The identification and detection of collective cell shape changes in an extensive collection of 3D time-lapse images of complex tissues is an important step in assaying such mechanisms but is a tedious and time-consuming task. Machine learning provides new opportunities to automatically detect cell shape changes. However, it is challenging to generate sufficient training samples for pattern identification through deep learning because of a limited amount of images and annotations.ResultWe present a deep learning approach with minimal well-annotated training samples and apply it to identify multicellular rosettes from 3D live images of the Caenorhabditis elegans embryo with fluorescently labelled cell membranes. Our strategy is to combine two approaches, namely, feature transfer and generative adversarial networks (GANs), to boost image classification with small training samples. Specifically, we use a GAN framework and conduct an unsupervised training to capture the general characteristics of cell membrane images with 11,250 unlabelled images. We then transfer the structure of the GAN discriminator into a new Alex-style neural network for further learning with several dozen labelled samples. Our experiments showed that with 10-15 well-labelled rosette images and 30-40 randomly selected non-rosette images our approach can identify rosettes with over 80% accuracy and capture over 90% of the model accuracy achieved with a training dataset that is five times larger. We also established a public benchmark dataset for rosette detection. This GAN-based transfer approach can be applied to study other cellular structures with minimal training [email protected], [email protected]

scholarly journals Erythrocyte morphology reflects the transbilayer distribution of incorporated phospholipids.

1989 ◽  
Vol 108 (4) ◽  
pp. 1375-1385 ◽  
Author(s):  
D L Daleke ◽  
W H Huestis
Keyword(s):  
Cell Morphology ◽  
Cell Shape ◽  
Shape Change ◽  
Cell Protein ◽  
Second Phase ◽  
Erythrocyte Morphology ◽  
Intracellular Magnesium ◽  
Cell Shape Changes ◽  
Protein Sulfhydryl Groups ◽  
Shape Changes

The transbilayer distribution of exogenous phospholipids incorporated into human erythrocytes is monitored through cell morphology changes and by the extraction of incorporated 14C-labeled lipids. Dilauroylphosphatidylserine (DLPS) and dilauroylphosphatidylcholine (DLPC) transfer spontaneously from sonicated unilamellar vesicles to erythrocytes, inducing a discocyte-to-echinocyte shape change within 5 min. DLPC-induced echinocytes revert slowly (t1/2 approximately 8 h) to discocytes, but DLPS-treated cells revert rapidly (10-20 min) to discocytes and then become invaginate stomatocytes. The second phase of the phosphatidylserine (PS)-induced shape change, conversion of echinocytes to stomatocytes, can be inhibited by blocking cell protein sulfhydryl groups or by depleting intracellular ATP or magnesium (Daleke, D. L., and W. H. Huestis. 1985. Biochemistry. 24:5406-5416). These cell shape changes are consistent with incorporation of phosphatidylcholine (PC) and PS into the membrane outer monolayer followed by selective and energy-dependent translocation of PS to the membrane inner monolayer. This hypothesis is explored by correlating cell shape with the fraction of the exogenous lipid accessible to extraction into phospholipid vesicles. Upon exposure to recipient vesicles, DLPC-induced echinocytes revert to discoid forms within 5 min, concomitant with the removal of most (88%) of the radiolabeled lipid. On further incubation, 97% of the foreign PC transfers to recipient vesicles. Treatment of DLPS-induced stomatocytes with acceptor vesicles extracts foreign PS only partially (22%) and does not affect cell shape significantly. Cell treated with inhibitors of aminophospholipid translocation (sulfhydryl blockers or intracellular magnesium depletion) and then incubated with either DLPS or DLPC become echinocytic and do not revert to discocytic or stomatocytic shape for many hours. On treatment with recipient vesicles, these echinocytes revert to discocytes in both cases, with concomitant extraction of 88-99% of radiolabeled PC and 86-97% of radiolabeled PS. The accessibility of exogenous lipids to extraction is uniformly consistent with the transbilayer lipid distribution inferred from cell shape changes, indicating that red cell morphology is an accurate and sensitive reporter of the transbilayer partitioning of incorporated exogenous phospholipids.

scholarly journals From Energy to Cellular Force in the Cellular Potts Model

2019 ◽  
Author(s):  
Elisabeth G. Rens ◽  
Leah Edelstein-Keshet
Keyword(s):  
Potts Model ◽  
Cell Shape ◽  
Rho Gtpase ◽  
Single Cells ◽  
Simple Algorithm ◽  
Cellular Potts Model ◽  
Minimization Method ◽  
Cell Shapes ◽  
Cell Shape Changes ◽  
Shape Changes

AbstractSingle and collective cell dynamics, cell shape changes, and cell migration can be conveniently represented by the Cellular Potts Model, a computational platform based on minimization of a Hamiltonian while permitting stochastic fluctuations. Using the fact that a force field is easily derived from a scalar energy (F = −∇H), we develop a simple algorithm to associate effective forces with cell shapes in the CPM. We display the predicted forces for single cells of various shapes and sizes (relative to cell rest-area and cell rest-perimeter). While CPM forces are specified directly from the Hamiltonian on the cell perimeter, we infer internal forces using interpolation, and refine the results with smoothing. Predicted forces compare favorably with experimentally measured cellular traction forces. We show that a CPM model with internal signaling (such as Rho-GTPase-related contractility) can be associated with retraction-protrusion forces that accompany cell shape changes and migration. We adapt the computations to multicellular systems, showing, for example, the forces that a pair of swirling cells exert on one another, demonstrating that our algorithm works equally well for interacting cells. Finally, we show forces associated with the dynamics of classic cell-sorting experiments in larger clusters of model cells.Author summaryCells exert forces on their surroundings and on one another. In simulations of cell shape using the Cellular Potts Model (CPM), the dynamics of deforming cell shapes is traditionally represented by an energy-minimization method. We use this CPM energy, the Hamiltonian, to derive and visualize the corresponding forces exerted by the cells. We use the fact that force is the negative gradient of energy to assign forces to the CPM cell edges, and then extend the results to interior forces by interpolation. We show that this method works for single as well as multiple interacting model cells, both static and motile. Finally, we show favorable comparison between predicted forces and real forces measured experimentally.

Drosophila gastrulation: analysis of cell shape changes in living embryos by three-dimensional fluorescence microscopy

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 365-370 ◽  
Author(s):  
Z. Kam ◽  
J.S. Minden ◽  
D.A. Agard ◽  
J.W. Sedat ◽  
M. Leptin
Keyword(s):  
Cell Shape ◽  
Three Dimensional ◽  
Time Lapse ◽  
Second Phase ◽  
Fluorescent Markers ◽  
Ventral Furrow ◽  
Cell Shapes ◽  
Cell Shape Changes ◽  
Two Phases ◽  
Shape Changes

The first event of Drosophila gastrulation is the formation of the ventral furrow. This process, which leads to the invagination of the mesoderm, is a classical example of epithelial folding. To understand better the cellular changes and dynamics of furrow formation, we examined living Drosophila embryos using three-dimensional time-lapse microscopy. By injecting fluorescent markers that visualize cell outlines and nuclei, we monitored changes in cell shapes and nuclear positions. We find that the ventral furrow invaginates in two phases. During the first ‘preparatory’ phase, many prospective furrow cells in apparently random positions gradually begin to change shape, but the curvature of the epithelium hardly changes. In the second phase, when a critical number of cells have begun to change shape, the furrow suddenly invaginates. Our results suggest that furrow formation does not result from an ordered wave of cell shape changes, contrary to a model for epithelial invagination in which a wave of apical contractions causes invagination. Instead, it appears that cells change their shape independently, in a stochastic manner, and the sum of these individual changes alters the curvature of the whole epithelium.

scholarly journals Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation

2020 ◽  
Author(s):  
Joel Dokmegang ◽  
Moi Hoon Yap ◽  
Liangxiu Han ◽  
Matteo Cavaliere ◽  
René Doursat
Keyword(s):  
Cell Shape ◽  
Computational Modelling ◽  
Tissue Level ◽  
Tissue Mechanics ◽  
Apical Surface ◽  
Biological Cell ◽  
Agent Based ◽  
Cell Shape Changes ◽  
Theoretical Evidence ◽  
Shape Changes

AbstractUnderstanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast and trophectoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a “cup”. Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG#, an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behaviours in silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is sufficient to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed dictates the cup shape of the epiblast and fosters its movement towards the uterine tissue. Together, these results offer mechanical insights into mouse implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.Author summaryComputational modelling is increasingly used in the context of biological development. Here we propose a novel agent-based model of biological cell and tissue mechanics to investigate important morphological changes during mouse embryo implantation. Our model is able to replicate key biological cell shape changes and tissue-level behaviour. Simulating mouse implantation with this model, we bring theoretical support to previous experimental observations that lumenogenesis in the epiblast is driven by repulsion, and provide theoretical evidence that changes in epiblast shape during implantation are regulated by trophectoderm development.

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