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Open accessJournal ArticleDOI: 10.1007/S00285-021-01550-0

Spots, stripes, and spiral waves in models for static and motile cells : GTPase patterns in cells.

04 Mar 2021-Journal of Mathematical Biology (Springer Berlin Heidelberg)-Vol. 82, Iss: 4, pp 28
Abstract: The polarization and motility of eukaryotic cells depends on assembly and contraction of the actin cytoskeleton and its regulation by proteins called GTPases. The activity of GTPases causes assembly of filamentous actin (by GTPases Cdc42, Rac), resulting in protrusion of the cell edge. Mathematical models for GTPase dynamics address the spontaneous formation of patterns and nonuniform spatial distributions of such proteins in the cell. Here we revisit the wave-pinning model for GTPase-induced cell polarization, together with a number of extensions proposed in the literature. These include introduction of sources and sinks of active and inactive GTPase (by the group of A. Champneys), and negative feedback from F-actin to GTPase activity. We discuss these extensions singly and in combination, in 1D, and 2D static domains. We then show how the patterns that form (spots, waves, and spirals) interact with cell boundaries to create a variety of interesting and dynamic cell shapes and motion.

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Topics: Actin cytoskeleton (60%), Filamentous actin (58%), GTPase (53%) ... read more
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6 results found


Open accessJournal ArticleDOI: 10.3390/BIOM11060824
31 May 2021-
Abstract: Among oral tissues, the periodontium is permanently subjected to mechanical forces resulting from chewing, mastication, or orthodontic appliances. Molecularly, these movements induce a series of subsequent signaling processes, which are embedded in the biological concept of cellular mechanotransduction (MT). Cell and tissue structures, ranging from the extracellular matrix (ECM) to the plasma membrane, the cytosol and the nucleus, are involved in MT. Dysregulation of the diverse, fine-tuned interaction of molecular players responsible for transmitting biophysical environmental information into the cell’s inner milieu can lead to and promote serious diseases, such as periodontitis or oral squamous cell carcinoma (OSCC). Therefore, periodontal integrity and regeneration is highly dependent on the proper integration and regulation of mechanobiological signals in the context of cell behavior. Recent experimental findings have increased the understanding of classical cellular mechanosensing mechanisms by both integrating exogenic factors such as bacterial gingipain proteases and newly discovered cell-inherent functions of mechanoresponsive co-transcriptional regulators such as the Yes-associated protein 1 (YAP1) or the nuclear cytoskeleton. Regarding periodontal MT research, this review offers insights into the current trends and open aspects. Concerning oral regenerative medicine or weakening of periodontal tissue diseases, perspectives on future applications of mechanobiological principles are discussed.

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Topics: Mechanobiology (51%), Regeneration (biology) (51%)

4 Citations


Open accessJournal ArticleDOI: 10.1098/RSTA.2020.0268
Abstract: In the nearly seven decades since the publication of Alan Turings work on morphogenesis, enormous progress has been made in understanding both the mathematical and biological aspects of his propose...

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Topics: Turing (61%)

2 Citations


Open accessJournal ArticleDOI: 10.1371/JOURNAL.PONE.0248293
18 Mar 2021-PLOS ONE
Abstract: The distribution of signaling molecules following mechanical or chemical stimulation of a cell defines cell polarization, with regions of high active Cdc42 at the front and low active Cdc42 at the rear. As reaction-diffusion phenomena between signaling molecules, such as Rho GTPases, define the gradient dynamics, we hypothesize that the cell shape influences the maintenance of the "front-to-back" cell polarization patterns. We investigated the influence of cell shape on the Cdc42 patterns using an established computational polarization model. Our simulation results showed that not only cell shape but also Cdc42 and Rho-related (in)activation parameter values affected the distribution of active Cdc42. Despite an initial Cdc42 gradient, the in silico results showed that the maximal Cdc42 concentration shifts in the opposite direction, a phenomenon we propose to call "reverse polarization". Additional in silico analyses indicated that "reverse polarization" only occurred in a particular parameter value space that resulted in a balance between inactivation and activation of Rho GTPases. Future work should focus on a mathematical description of the underpinnings of reverse polarization, in combination with experimental validation using, for example, dedicated FRET-probes to spatiotemporally track Rho GTPase patterns in migrating cells. In summary, the findings of this study enhance our understanding of the role of cell shape in intracellular signaling.

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Topics: Cell polarity (50%)

1 Citations


Open accessJournal ArticleDOI: 10.1038/S41598-021-99029-X
30 Sep 2021-Scientific Reports
Abstract: The Rho family GTPases are molecular switches that regulate cytoskeletal dynamics and cell movement through a complex spatiotemporal organization of their activity. In Patiria miniata (starfish) oocytes under in vitro experimental conditions (with overexpressed Ect2, induced expression of Δ90 cyclin B, and roscovitine treatment), such activity generates multiple co-existing regions of coherent propagation of actin waves. Here we use computational modeling to investigate the development and properties of such wave domains. The model reveals that the formation of wave domains requires a balance between the activation and inhibition in the Rho signaling motif. Intriguingly, the development of the wave domains is preceded by a stage of low-activity quasi-static patterns, which may not be readily observed in experiments. Spatiotemporal patterns of this stage and the different paths of their destabilization define the behavior of the system in the later high-activity (observable) stage. Accounting for a strong intrinsic noise allowed us to achieve good quantitative agreement between simulated dynamics in different parameter regimes of the model and different wave dynamics in Patiria miniata and wild type Xenopus laevis (frog) data. For quantitative comparison of simulated and experimental results, we developed an automated method of wave domain detection, which revealed a sharp reversal in the process of pattern formation in starfish oocytes. Overall, our findings provide an insight into spatiotemporal regulation of complex and diverse but still computationally reproducible cell-level actin dynamics.

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Open accessPosted Content
Yue Liu1, Philip K. Maini, Ruth E. BakerInstitutions (1)
Abstract: In certain biological contexts, such as the plumage patterns of birds and stripes on certain species of fishes, pattern formation takes place behind a so-called ``wave of competency". Currently, the effects of a wave of competency on the patterning outcome is not well-understood. In this study, we use Turing's diffusion-driven instability model to study pattern formation behind a wave of competency, under a range of wave speeds. Numerical simulations show that in one spatial dimension a slower wave speed drives a sequence of peak splittings in the pattern, whereas a higher wave speed leads to peak insertions. In two spatial dimensions, we observe stripes that are either perpendicular or parallel to the moving boundary under slow or fast wave speeds, respectively. We argue that there is a correspondence between the one- and two-dimensional phenomena, and that pattern formation behind a wave of competency can account for the pattern organization observed in many biological systems.

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Topics: Pattern formation (50%)

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37 results found


Journal ArticleDOI: 10.1098/RSTB.1952.0012
A. M. Turing1Institutions (1)
Abstract: It is suggested that a system of chemical substances, called morphogens, reacting together and diffusing through a tissue, is adequate to account for the main phenomena of morphogenesis. Such a system, although it may originally be quite homogeneous, may later develop a pattern or structure due to an instability of the homogeneous equilibrium, which is triggered off by random disturbances. Such reaction-diffusion systems are considered in some detail in the case of an isolated ring of cells, a mathematically convenient, though biologically unusual system. The investigation is chiefly concerned with the onset of instability. It is found that there are six essentially different forms which this may take. In the most interesting form stationary waves appear on the ring. It is suggested that this might account, for instance, for the tentacle patterns on Hydra and for whorled leaves. A system of reactions and diffusion on a sphere is also considered. Such a system appears to account for gastrulation. Another reaction system in two dimensions gives rise to patterns reminiscent of dappling. It is also suggested that stationary waves in two dimensions could account for the phenomena of phyllotaxis. The purpose of this paper is to discuss a possible mechanism by which the genes of a zygote may determine the anatomical structure of the resulting organism. The theory does not make any new hypotheses; it merely suggests that certain well-known physical laws are sufficient to account for many of the facts. The full understanding of the paper requires a good knowledge of mathematics, some biology, and some elementary chemistry. Since readers cannot be expected to be experts in all of these subjects, a number of elementary facts are explained, which can be found in text-books, but whose omission would make the paper difficult reading.

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9,015 Citations


Open accessBook
01 Jan 1995-
Abstract: Introduction to Dynamical Systems * Topological Equivalence, Bifurcations, and Structural Stability of Dynamical Systems * One-Parameter Bifurcations of Equilibria in Continuous-Time Systems * One-Parameter Bifurcations of Fixed Points in Discrete-Time Systems * Bifurcations of Equilibria and Periodic Orbits in n-Dimensional Systems * Bifurcations of Orbits Homoclinic and Heteroclinic to Hyperbolic Equilibria * Other One-Parameter Bifurcations in Continuous-Time Systems * Two-Parameter Bifurcations of Equilibria in Continuous-Time Dynamical Systems * Two-Parameter Bifurcations of Fixed Points in Discrete-Time Dynamical Systems * Numerical Analysis of Bifurcations * A: Basic Notions from Algebra, Analysis, and Geometry * References * Index.

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4,859 Citations


MonographDOI: 10.1137/1.9780898719147
01 Feb 2005-
Abstract: Part I. Discrete Process in Biology: 1. The theory of linear difference equations applied to population growth 2. Nonlinear difference equations 3. Applications of nonlinear difference equations to population biology Part II. Continuous Processes and Ordinary Differential Equations: 4. An introduction to continuous models 5. Phase-plane methods and qualitative solutions 6. Applications of continuous models to population dynamics 7. Models for molecular events 8. Limit cycles, oscillations, and excitable systems Part III. Spatially Distributed Systems and Partial Differential Equation Models: 9. An introduction to partial differential equations and diffusion in biological settings 10. Partial differential equation models in biology 11. Models for development and pattern formation in biological systems Selected answers Author index Subject index.

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1,861 Citations


Open accessBook
G. Bard Ermentrout1Institutions (1)
01 Jan 1987-
Abstract: List of figures Preface 1. Installation 2 A Very Brief Tour of XPPAUT 3. Writing ODE Files for Differential Equations 4. XPPAUT in the Classroom 5. More Advanced Diffferential Equations 6. Spatial Problems, PDEs, and BVPs 7. Using AUTO. Bifurcation and Continuation 8. Animation 9 Tricks and Advanced Methods Appendix A. Colors and Linestyles Appendix B. The Options Appendix C. Numerical Methods Appendix D. Structure of ODE Files Appendix E. Complete Command List Appendix F. Error Messages Appendix G. Cheat Sheet References IndexAppendix C. Numerical Methods Appendix D. Structure of ODE Files Appendix E. Complete Command List Appendix F. Error Messages Appendix G. Cheat Sheet References Index.

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1,606 Citations


Open accessDOI: 10.11588/ANS.2015.100.20553
Martin Sandve Alnæs1, Jan Blechta2, Johan Hake1, August Johansson1  +6 moreInstitutions (4)
07 Dec 2015-
Abstract: The FEniCS Project is a collaborative project for the development of innovative concepts and tools for automated scientific computing, with a particular focus on the solution of differential equations by finite element methods. The FEniCS Projects software consists of a collection of interoperable software components, including DOLFIN, FFC, FIAT, Instant, UFC, UFL, and mshr. This note describes the new features and changes introduced in the release of FEniCS version 1.5.

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1,200 Citations


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