Morphogenesis and proportionate growth: A finite element investigation of surface growth with coupled diffusion

Modeling the spontaneous evolution of morphology in natural systems and its preservation by proportionate growth remains a major scientific challenge. Yet, it is conceivable that if the basic mechanisms of growth and the coupled kinetic laws that orchestrate their function are accounted for, a minimal theoretical model may exhibit similar growth behaviors. The ubiquity of surface growth, a mechanism by which material is added or removed on the boundaries of the body, has motivated the development of theoretical models, which can capture the diffusion-coupled kinetics that govern it. However, due to their complexity, application of these models has been limited to simplified geometries. In this paper, we tackle these complexities by developing a finite element framework to study the diffusion-coupled growth and morphogenesis of finite bodies formed on uniform and flat substrates. We find that in this simplified growth setting, the evolving body exhibits a sequence of distinct growth stages that are reminiscent of natural systems, and appear spontaneously without any externally imposed regulation or coordination. The computational framework developed in this work can serve as the basis for future models that are able to account for growth in arbitrary geometrical settings, and can shed light on the basic physical laws that orchestrate growth and morphogenesis in the natural world

A parallelized cellular Potts model that enables simulations at tissue scale

The Cellular Potts Model (CPM) is a widely used simulation paradigm for systems of interacting cells that has been used to study scenarios ranging from plant development to morphogenesis, tumour growth and cell migration. Despite their wide use, CPM simulations are considered too computationally intensive for three-dimensional (3D) models at organ scale. CPMs have been difficult to parallelise because of their inherently sequential update scheme. Here, we present a Graphical Processing Unit (GPU)-based parallelisation scheme that preserves local update statistics and is up to 3-4 orders of magnitude faster than serial implementations. We show several examples where our scheme preserves simulation behaviors that are drastically altered by existing parallelisation methods. We use our framework to construct tissue-scale models of liver and lymph node environments containing millions of cells that are directly based on microscopy-imaged tissue structures. Thus, our GPU-based CPM framework enables in silico studies of multicellular systems of unprecedented scale.Comment: 29 pages, 11 figures, 3 table

Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis. © 2013 Lee et al

Applications of Biological Cell Models in Robotics

In this paper I present some of the most representative biological models applied to robotics. In particular, this work represents a survey of some models inspired, or making use of concepts, by gene regulatory networks (GRNs): these networks describe the complex interactions that affect gene expression and, consequently, cell behaviour

Surface and bulk stresses drive morphological changes in fibrous microtissues

Engineered fibrous tissues consisting of cells encapsulated within collagen gels are widely used three-dimensional in vitro models of morphogenesis and wound healing. Although cell-mediated matrix remodeling that occurs within these scaffolds has been extensively studied, less is known about the mesoscale physical principles governing the dynamics of tissue shape. Here, we show both experimentally and by using computer simulations how surface contraction through the development of surface stresses (analogous to surface tension in fluids) coordinates with bulk contraction to drive shape evolution in constrained three-dimensional microtissues. We used microelectromechanical systems technology to generate arrays of fibrous microtissues and robot-assisted microsurgery to perform local incisions and implantation. We introduce a technique based on phototoxic activation of a small molecule to selectively kill cells in a spatially controlled manner. The model simulations, which reproduced the experimentally observed shape changes after surgical and photochemical operations, indicate that fitting of only bulk and surface contractile moduli is sufficient for the prediction of the equilibrium shape of the microtissues. The computational and experimental methods we have developed provide a general framework to study and predict the morphogenic states of contractile fibrous tissues under external loading at multiple length scales.Published versio

Implementing vertex dynamics models of cell populations in biology within a consistent computational framework

The dynamic behaviour of epithelial cell sheets plays a central role during development, growth, disease and wound healing. These processes occur as a result of cell adhesion, migration, division, differentiation and death, and involve multiple processes acting at the cellular and molecular level. Computational models offer a useful means by which to investigate and test hypotheses about these processes, and have played a key role in the study of cell–cell interactions. However, the necessarily complex nature of such models means that it is difficult to make accurate comparison between different models, since it is often impossible to distinguish between differences in behaviour that are due to the underlying model assumptions, and those due to differences in the in silico implementation of the model. In this work, an approach is described for the implementation of vertex dynamics models, a discrete approach that represents each cell by a polygon (or polyhedron) whose vertices may move in response to forces. The implementation is undertaken in a consistent manner within a single open source computational framework, Chaste, which comprises fully tested, industrial-grade software that has been developed using an agile approach. This framework allows one to easily change assumptions regarding force generation and cell rearrangement processes within these models. The versatility and generality of this framework is illustrated using a number of biological examples. In each case we provide full details of all technical aspects of our model implementations, and in some cases provide extensions to make the models more generally applicable

Digital Tectonics as a Morphogenetic Process

p. 938-948Tectonics is a seminal concept that defines the nature of the relationship between architecture and its structural properties. The changing definition of the symbiotic relationship between structural engineering and architectural design may be considered one of the formative influences on the conceptual evolution of tectonics in different historical periods. Recent developments in the field of morphogenesis, digital media, theories techniques and methods of digital design have contributed a new models of integration between structure, material and form in digital tectonics. The objective of this paper is to propose and define tectonics as a model of morphogenetic process. The paper identifies and presents the manner in which theory and emerging concepts of morphogenesis as well as digital models of design are contributing to this new model. The paper first analyzes the historical evolution of tectonics as a concept and characterizes the emergence of theoretical framework reflected in concepts and terms related to morphogenesis.Oxman, R. (2010). Digital Tectonics as a Morphogenetic Process. Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/695

Incorporating chemical signalling factors into cell-based models of growing epithelial tissues

In this paper we present a comprehensive computational framework within which the effects of chemical signalling factors on growing epithelial tissues can be studied. The method incorporates a vertex-based cell model, in conjunction with a solver for the governing chemical equations. The vertex model provides a natural mesh for the finite element method (FEM), with node movements determined by force laws. The arbitrary Lagrangian–Eulerian formulation is adopted to account for domain movement between iterations. The effects of cell proliferation and junctional rearrangements on the mesh are also examined. By implementing refinements of the mesh we show that the finite element (FE) approximation converges towards an accurate numerical solution. The potential utility of the system is demonstrated in the context of Decapentaplegic (Dpp), a morphogen which plays a crucial role in development of the Drosophila imaginal wing disc. Despite the presence of a Dpp gradient, growth is uniform across the wing disc. We make the growth rate of cells dependent on Dpp concentration and show that the number of proliferation events increases in regions of high concentration. This allows hypotheses regarding mechanisms of growth control to be rigorously tested. The method we describe may be adapted to a range of potential application areas, and to other cell-based models with designated node movements, to accurately probe the role of morphogens in epithelial tissues

A modified Oster-Murray-Harris mechanical model of morphogenesis

There are two main modeling paradigms for biological pattern formation in developmental biology: chemical prepattern models and cell aggregation models. This paper focuses on an example of a cell aggregation model, the mechanical model developed by Oster, Murray, and Harris [Development, 78 (1983), pp. 83--125]. We revisit the Oster--Murray--Harris model and find that, due to the infinitesimal displacement assumption made in the original version of this model, there is a restriction on the types of boundary conditions that can be prescribed. We derive a modified form of the model which relaxes the infinitesimal displacement assumption. We analyze the dynamics of this model using linear and multiscale nonlinear analysis and show that it has the same linear behavior as the original Oster--Murray--Harris model. Nonlinear analysis, however, predicts that the modified model will allow for a wider range of parameters where the solution evolves to a bounded steady state. The results from both analyses are verified through numerical simulations of the full nonlinear model in one and two dimensions. The increased range of boundary conditions that are well-posed, as well as a wider range of parameters that yield bounded steady states, renders the modified model more applicable to, and more robust for, comparisons with experiments