scholarly journals Epithelial colonies in vitro elongate through collective effects

2019 ◽  
Author(s):  
Jordi Comelles ◽  
SS Soumya ◽  
Linjie Lu ◽  
Emilie Le Maout ◽  
S. Anvitha ◽  
...  
Keyword(s):  
Cell Elongation ◽  
Multiple Scales ◽  
Collective Effects ◽  
Global Symmetry ◽  
Average Cell ◽  
Morphogen Gradients ◽  
Oriented Cell Division ◽  
Deformation Kinematics ◽  
External Time

AbstractEpithelial tissues of the developing embryos elongate by different mechanisms, such as neighbor exchange, cell elongation, and oriented cell division. Since autonomous tissue self-organization is influenced by external cues such as morphogen gradients or neighboring tissues, it is difficult to distinguish intrinsic from directed tissue behavior. The mesoscopic processes leading to the different mechanisms remain elusive. Here, we study the spontaneous elongation behavior of spreading circular epithelial colonies in vitro. By quantifying deformation kinematics at multiple scales, we report that global elongation happens primarily due to cell elongations, and its direction correlates with the anisotropy of the average cell elongation. By imposing an external time-periodic stretch, the axis of this global symmetry breaking can be modified and elongation occurs primarily due to orientated neighbor exchange. These different behaviors are confirmed using a vertex model for collective cell behavior, providing a framework for understanding autonomous tissue elongation and its origins.

scholarly journals Epithelial colonies in vitro elongate through collective effects

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jordi Comelles ◽  
Soumya S S ◽  
Linjie Lu ◽  
Emilie Le-Maout ◽  
Sudakar Anvitha ◽  
...  
Keyword(s):  
Cell Elongation ◽  
Multiple Scales ◽  
Collective Effects ◽  
Global Symmetry ◽  
Average Cell ◽  
Morphogen Gradients ◽  
Oriented Cell Division ◽  
Deformation Kinematics ◽  
External Time

Epithelial tissues of the developing embryos elongate by different mechanisms, such as neighbor exchange, cell elongation, and oriented cell division. Since autonomous tissue self-organization is influenced by external cues such as morphogen gradients or neighboring tissues, it is difficult to distinguish intrinsic from directed tissue behavior. The mesoscopic processes leading to the different mechanisms remain elusive. Here, we study the spontaneous elongation behavior of spreading circular epithelial colonies in vitro. By quantifying deformation kinematics at multiple scales, we report that global elongation happens primarily due to cell elongations, and its direction correlates with the anisotropy of the average cell elongation. By imposing an external time-periodic stretch, the axis of this global symmetry breaking can be modified and elongation occurs primarily due to orientated neighbor exchange. These different behaviors are confirmed using a vertex model for collective cell behavior, providing a framework for understanding autonomous tissue elongation and its origins.

scholarly journals In vivo functional diversity of midbrain dopamine neurons within identified axonal projections

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Navid Farassat ◽  
Kauê Machado Costa ◽  
Strahinja Stojanovic ◽  
Stefan Albert ◽  
Lora Kovacheva ◽  
...  
Keyword(s):  
Functional Diversity ◽  
Multiple Scales ◽  
Dopamine Neurons ◽  
Unit Recording ◽  
Axonal Projections ◽  
Intact Brain ◽  
Functional Topography ◽  
Midbrain Dopamine

Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and labelling in mouse brain to create an in vivo functional topography of the midbrain DA system. We identified differences in burst firing among DA neurons projecting to dorsolateral striatum. Bursting also differentiated DA neurons in the medial substantia nigra (SN) projecting either to dorsal or ventral striatum. We found differences in mean firing rates and pause durations among ventral tegmental area (VTA) DA neurons projecting to lateral or medial shell of nucleus accumbens. Our data establishes a high-resolution functional in vivo landscape of midbrain DA neurons.

scholarly journals Self-organized cell migration across scales – from single cell movement to tissue formation

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
pp. dev191767
Author(s):  
Jessica Stock ◽  
Andrea Pauli
Keyword(s):  
Cell Migration ◽  
Multiple Scales ◽  
Single Cells ◽  
Cell Movement ◽  
Biological Response ◽  
Collective Cell Migration ◽  
Theoretical Concepts ◽  
Self Organizing

ABSTRACTSelf-organization is a key feature of many biological and developmental processes, including cell migration. Although cell migration has traditionally been viewed as a biological response to extrinsic signals, advances within the past two decades have highlighted the importance of intrinsic self-organizing properties to direct cell migration on multiple scales. In this Review, we will explore self-organizing mechanisms that lay the foundation for both single and collective cell migration. Based on in vitro and in vivo examples, we will discuss theoretical concepts that underlie the persistent migration of single cells in the absence of directional guidance cues, and the formation of an autonomous cell collective that drives coordinated migration. Finally, we highlight the general implications of self-organizing principles guiding cell migration for biological and medical research.

scholarly journals 3D Tissue elongation via ECM stiffness-cued junctional remodeling

2018 ◽  
Author(s):  
Dong-Yuan Chen ◽  
Justin Crest ◽  
Sebastian J. Streichan ◽  
David Bilder
Keyword(s):  
Basement Membrane ◽  
Cell Shape ◽  
Cell Dynamics ◽  
Src Tyrosine Kinase ◽  
Average Cell ◽  
Cellular Behavior ◽  
Cell Behaviors ◽  
Oriented Cell Division ◽  
Morphometric Analyses ◽  
Membrane Stiffness

ABSTRACTOrgans are sculpted by extracellular as well as cell-intrinsic forces, but how collective cell dynamics are orchestrated in response to microenvironmental cues is poorly understood. Here we apply advanced image analysis to reveal ECM-responsive cell behaviors that drive elongation of the Drosophila follicle, a model 3D system in which basement membrane stiffness instructs tissue morphogenesis. Through in toto morphometric analyses of WT and ‘round egg’ mutants, we find that neither changes in average cell shape nor oriented cell division are required for appropriate organ shape. Instead, a major element is a reorientation of elongated cells at the follicle anterior. Polarized reorientation is regulated by mechanical cues from the basement membrane, which are transduced by the Src tyrosine kinase to alter junctional E-cadherin trafficking. This mechanosensitive cellular behavior represents a conserved mechanism that can elongate ‘edgeless’ tubular epithelia in a process distinct from those that elongate bounded, planar epithelia.

Effects of Blood Flow on Radiofrequency Ablation of Tumors: Finite Elements and In Vitro Models

2003 ◽  
Author(s):  
Juan R. Cebral ◽  
Orlando Soto ◽  
Robert J. Lutz ◽  
Bradford J. Wood
Keyword(s):  
Blood Flow ◽  
Radiofrequency Ablation ◽  
Saline Solution ◽  
Numerical Models ◽  
In Vitro Models ◽  
Collective Effects ◽  
Ablation Lesion ◽  
Thermal Flow ◽  
Flow Process

The efficacy of radiofrequency ablation (RFA) treatments depends on the ability to ablate tumors completely while minimizing the damage to healthy tissue. Tissue cooling due to blood flow is an important factor affecting the size and shape of the ablation lesion. In this paper a new methodology for finite element modeling of the coupled electrical-thermal-flow process during RFA is presented. Our formulation treats heat losses due to blood flow explicitly rather than approximating the collective effects of blood vessles as a heat sink. Numerical models were compared to in vitro models using egg whites to simulate human tissue and a straight cylinder filled with a saline solution to simulate blood. Asymmetric burns were obtained close to the simulated blood vessels. Numerical results closely match the in vitro models.

The utilization of an inhibitor of spermidine and spermine synthesis as a tool for the study of the determination of cavitation in the preimplantation mouse embryo

Development ◽  
1979 ◽  
Vol 53 (1) ◽  
pp. 145-162
Author(s):  
H. Alexandre
Keyword(s):  
Biological Clock ◽  
Duration Of Treatment ◽  
Experimental Conditions ◽  
Cell Stage ◽  
Cytoplasmic Factor ◽  
Average Cell ◽  
Length Of Treatment ◽  
Preimplantation Mouse ◽  
The One

The inhibition of spermidine and spermine synthesis by methylglyoxal-Bis(guanylhydrazone) (MeGAG) at concentrations of 5, 10 and 20 µM, induces a reversible metabolic quiescence of mouse embryos, cultured in vitro from the 2-cell stage, at an average of 10·2, 8·5 and 6·9 cell stages respectively. In contrast, the inhibition of putrescine synthesis by α-methylornithine (α-MeOrn) at concentrations up to 10 mM fails to inhibit blastocyst formation, as shown previously. Complete reversibility of this induced arrest of development is observed for treatments up to 31 h with MeGAG at 10 µM. In agreement with the biological clock theory of Smith & MacLaren's hypothesis, the delay in cavitation is proportional to the length of treatment. However, the average cell numbers of the ‘delayed nascent blastocysts’ of all treated embryos (21·8–24·2) are consistently lower than that of control embryos (33·6) irrespective of the duration of treatment. It seems therefore that under some experimental conditions, DNA and chromosome replication on the one hand and cytoplasmic maturation on the other may be desynchronized. This suggests a role for a cytoplasmic factor in the induction of cavitation.

Predicting drug synergy for precision medicine using network biology and machine learning

2019 ◽  
Vol 17 (02) ◽  
pp. 1950012 ◽  
Author(s):  
Ali Cuvitoglu ◽  
Joseph X. Zhou ◽  
Sui Huang ◽  
Zerrin Isik
Keyword(s):  
Machine Learning ◽  
Biological Network ◽  
Network Biology ◽  
Drug Combinations ◽  
Classification Model ◽  
Molecular Networks ◽  
Collective Effects ◽  
Cancer Drug ◽  
Drug Synergy

Identification of effective drug combinations for patients is an expensive and time-consuming procedure, especially for in vitro experiments. To accelerate the synergistic drug discovery process, we present a new classification model to identify more effective anti-cancer drug pairs using in silico network biology approach. Based on the hypotheses that the drug synergy comes from the collective effects on the biological network, therefore, we developed six network biology features, including overlap and distance of drug perturbation network, that were derived by using individual drug-perturbed transcriptome profiles and the relevant biological network analysis. Using publicly available drug synergy databases and three machine-learning (ML) methods, the model was trained to discriminate the positive (synergistic) and negative (nonsynergistic) drug combinations. The proposed models were evaluated on the test cases to predict the most promising network biology feature, which is the network degree activity, i.e. the synergistic effect between drug pairs is mainly accounted by the complementary signaling pathways or molecular networks from two drugs.

THE ROLE OF ENDO-1,4-BETA-GLUCANASE IN PLANT CELL ELONGATION. IN-VITRO STUDIES OF PEACH POLLEN

1993 ◽  
pp. 225-227
Author(s):  
O. Shoseyov ◽  
M. Dekel-Reichenbach
Keyword(s):  
Plant Cell ◽  
Cell Elongation ◽  
In Vitro Studies ◽  
Beta Glucanase

scholarly journals Differentiation of a teratocarcinoma line: preferential development of cholinergic neurons.

1981 ◽  
Vol 88 (1) ◽  
pp. 57-66 ◽  
Author(s):  
S E Pfeiffer ◽  
H Jakob ◽  
K Mikoshiba ◽  
P Dubois ◽  
J L Guenet ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Cholinergic Neurons ◽  
Carcinoma Cells ◽  
Sodium Influx ◽  
Average Cell ◽  
Transmission Electron ◽  
Neuronal Processes ◽  
Embryonic Antigen ◽  
Average Cell Volume

A line of embryonal carcinoma cells, PCC7-S, established in vitro from a spontaneous testicular teratocarcinoma, has been studied. Upon removing the cells from a low density monolayer culture system and permitting the cells to form aggregates in suspension, we observed a change of several physical and biochemical parameters: (a) reduction in average cell volume, (b) blockage and accumulation of cells in G1, (c) rise in secreted protease activity, (d) rise in acetylcholinesterase and choline acetyltransferase activities, and (e) disappearance of embryonic antigen F9. Although PCC7 aggregates did not undergo substantial morphological changes while suspended, when aggregates 4 or more days old were allowed to attach to plastic tissue culture dishes, substantial neurite outgrowth occurred over the next 1-3 d. This process was markedly enhanced by the addition to the growth medium of carboxymethylcellulose and inhibitors of DNA synthesis. Transmission electron microscopy disclosed a neurite ultrastructure consistent with that of neuronal processes. A veratridine-stimulated, tetrodotoxin-blocked sodium influx of 100 nmol/min per mg protein was also observed in these differentiated surface cultures. This cell line is discussed in terms of its utility for the study of early events leading to a commitment to cellular differentiation, as well as for the investigation of terminal differentiation to cholinergic neurons.

Requirements for the Manufacturing of Scaffold Biomaterial With Features at Multiple Scales

2005 ◽  
Author(s):  
I. M. Sebastine ◽  
D. J. Williams
Keyword(s):  
Tissue Engineering ◽  
Multiple Scales ◽  
Cell Attachment ◽  
Structural Parameters ◽  
Complex Function ◽  
Three Dimensional ◽  
Cell Orientation ◽  
Length Scales

Tissue engineering aims to restore the complex function of diseased tissue using cells and scaffold materials. Tissue engineering scaffolds are three-dimensional (3D) structures that assist in the tissue engineering process by providing a site for cells to attach, proliferate, differentiate and secrete an extra-cellular matrix, eventually leading cells to form a neo-tissue of predetermined, three-dimensional shape and size. For a scaffold to function effectively, it must possess the optimum structural parameters conducive to the cellular activities that lead to tissue formation; these include cell penetration and migration into the scaffold, cell attachment onto the scaffold substrate, cell spreading and proliferation and cell orientation. In vivo, cells are organized in functional tissue units that repeat on the order of 100 μm. Fine scaffold features have been shown to provide control over attachment, migration and differentiation of cells. In order to design such 3D featured constructs effectively understanding the biological response of cells across length scales from nanometer to millimeter range is crucial. Scaffold biomaterials may need to be tailored at three different length scales: nanostructure (<1μm), microstructure (<20–100μm), and macrostructure (>100μm) to produce biocompatible and biofunctional scaffolds that closely resemble the extracellular matrix (ECM) of the natural tissue environment and promote cell adhesion, attachment, spreading, orientation, rate of movement, and activation. Identification of suitable fabrication techniques for manufacturing scaffolds with the required features at multiple scales is a significant challenge. This review highlights the effect and importance of the features of scaffolds that can influence the behaviour of cells/tissue at different length scales in vitro to increase our understanding of the requirements for the manufacture of functional 3D tissue constructs.

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