Simulating tissue mechanics with Agent Based Models: concepts and perspectives

International audienceIn this paper we present an overview of agent based models that are used to simulate mechanical and physiological phenomena in cells and tissues, and we discuss underlying concepts, limitations and future perspectives of these models. As the interest in cell and tissue mechanics increase, agent based models are becoming more common the modeling community. We overview the physical aspects, complexity, shortcomings and capabilities of the major agent based model categories: lattice-based models (cellular automata, lattice gas cellular automata, cellular Potts models), off-lattice models (center based models, deformable cell models, vertex models), and hybrid discrete-continuum models. In this way, we hope to assist future researchers in choosing a model for the phenomenon they want to model and understand. The article also contains some novel results

Influence of cell mechanics in embryonic bile duct lumen formation: insight from quantitative modeling

In biological and medical literature, alternative hypotheses for initial bile duct lumen formation during embryogenesis exist, which so far remained largely untested. Guided by the quantification of morphological features and expression of genes in developing bile ducts from embryonic mouse liver, these hypotheses were sharpened and data collected that permitted to develop a high resolution individual-based computational model to test the alternative hypotheses in silico. Simulations with this model suggest that successful bile duct lumen formation primarily requires the simultaneous contribution of directed cell division of cholangiocytes, local osmotic effects generated by salt excretion in the lumen, and temporally-controlled differentiation of hepatoblasts to cholangiocytes, with apical constriction of cholangiocytes only moderately affecting luminal size

Solving microscopic flow problems using Stokes equations in SPH

International audienceStarting from the Smoothed Particle Hydrodynamics method (SPH), we propose an alternative way to solve flow problems at a very low Reynolds number. The method is based on an explicit drop out of the inertial terms in the normal SPH equations, and solves the coupled system to find the velocities of the particles using the conjugate gradient method. The method will be called NSPH which refers to the noninertial character of the equations. Whereas the time-step in standard SPH formulations for low Reynolds numbers is linearly restricted by the inverse of the viscosity and quadratically by the particle resolution, the stability of the NSPH solution benefits from a higher viscosity and is independent of the particle resolution. Since this method allows for a much higher time-step, it solves creeping flow problems with a high resolution and a long timescale up to three orders of magnitude faster than SPH. In this paper, we compare the accuracy and capabilities of the new NSPH method to canonical SPH solutions considering a number of standard problems in fluid dynamics. In addition, we show that NSPH is capable of modeling more complex physical phenomena such as the motion of a red blood cell in plasm

Discrete element method models of deformable cells in 2D and 3D environments to explore traction generation mechanisms

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Modeling extracellular matrix viscoelasticity using smoothed particle hydrodynamics with improved boundary treatment

International audienceWe propose viscoelastic smoothed particle hydrodynamics (SPH) with extended boundary conditions as a new method to model the extracellular matrix (ECM) in contact with a migrating cell. The contact mechanics between a cell and ECM is modeled based on an existing boundary method in SPH that corrects for the well-known missing kernel support problem in Fluid Structure Interactions (FSI). This boundary method is here extended to allow the modeling of moving boundaries in contact with a viscoelastic solid. To validate the method, simulations are performed of tractions applied to a viscoelastic solid, Stokes flow around an array of square pillars, and indentation of a viscoelastic material with a circular indenter. By drop out of the inertial terms in the SPH equations of motion, the new SPH formulation allows to solve problems in a low Reynolds environment with a timestep independent of the particle spacing, permitting to model processes at the cellular scale (i.e. µm-scale). The potential of the method to capture cell–ECM interactions is demonstrated by simulation of a self propelling object that locally degrades the ECM by fluidizing it to permit migration. This should enable us to model and understand realistic cell–matrix interactions in the future

Study of the granular fertilizers and the centrifugal spreader using Discrete Element Method (DEM) simulations

Since the beginning of production of mineral fertilizers, the worldwide crop yield has been increased dramatically, supplying the food for the exponentially growing population. In the 90’s of the 20th century however, a major concern about the environmental implications of fertilizer spreading has been developed. Over-doses can harm the environment seriously, as well as the crop itself. As a consequence, the spreadability of fertilizer and the uniformity of the spread pattern has become an important topic in this part of agricultural engineering. In Europe, 90% of the fertilizer spreading applications are performed by centrifugal spreading. The popularity of this technique lies in their low price, easy maintenance, and large working width. However, its design is highly sensitive to machine characteristics as well as fertilizer particle properties and weather conditions (e.g. wind). As a consequence, research about the mechanism of spreading has become inevitable. A lot of effort on the influence of machine characteristics on the spread pattern has been done by Olieslagers (1997). In this thesis, the emphasis will be put on the study of fertilizer particles. These particles interact with the machine parts as well as with each other. Hereto, the “Discrete Element Method“ computational technique is introduced. Basically, DEM calculates all possible interaction between objects using force models based on spring – dashpot systems, and describes their motion using classical dynamics. By changing the physical properties of the individual particles, such a method allows a comprehensive study of the particle flow on a rotating disc. The physical properties of the fertilizer serve as the input parameters of the model. However, due to nature of fertilizer particles, they are hard to determine. Several techniques have been proposed in this thesis to provide either an accurate measurement or an acceptable estimation of these properties. The accuracy of the model will largely depend on value of the input parameter as well as the sensitivity to this parameter. Before trying to simulate the whole spreading process, the interaction of a single particle with the machine parts (e.g. disc, vanes,..) of the spreader is considered. This step is primordial since it allows a decomposition of the physical problem as well as an easy validation of the simulation model with experiments. Having obtained this insight, simulations of a particle flow on the disc (multi particle simulations) can be carried out. Both the performance of these simulations and the experimental validations are intensive tasks, requiring a lot of time. However, they are mandatory in order to get full insight in the parameters that affect the spread pattern and the predictive value of the model. Generally, it was found that the DEM simulations perform qualitatively well. The cause of the deviations (below 25%) between simulations and experiments remains uncertain but is likely to be found in the insufficient knowledge of the initial conditions of the particles (e.g. outflow of the bin) as well as the contact force mechanisms. In the light of the accuracy of the measured particle properties and the model output, a sensitivity study is carried out in this research. The main goal herby is to gain insight in the parameters that influence the spread pattern, and those who don’t. Although done in a qualitative way, such a study can provide valuable information for the manufacturer in the development of new fertilizer kinds or spreader designs. In this research, it was found that friction plays a crucial role in the dynamics of the particles on the disc, and the friction coefficients should be treated as velocity dependent parameters. An important part of the errors made by the model could be explained by this.-General introduction -The Discrete Element Method -Particle measuring methods as input for numerical models -Single particle simulations -Multi particle simulations -Model parameter sensitivity -Case study: DEM simulations of a new concept for lawn spreader -General conclusions and future outlinestatus: publishe

Discrete element simulations of the influence of fertiliser physical properties on the spread pattern from spinning disc spreaders

This paper describes a sensitivity study of the flow of granular fertiliser particles on a spinning disc using a discrete element model. The aim was to get a qualitative insight in the influences of individual physical properties of the particles (such as friction coefficient, restitution, and shape) as well as their bulk behaviour on the resulting spread pattern. The results show that certain particle properties, particularly friction coefficients, have a large influence on the spread pattern, and hence should examined carefully in the process of producing granular fertilisers, perhaps by particle coating, or taken into account when applying the fertiliser in the field. Other properties, such as particle stiffness hardly affect the results. Furthermore, it was shown that the friction coefficient and shape of a particle strongly interfere in their particular influence on the spread pattern. Overall, the discrete element model could provide a powerful instrument for the manufacturers in the development of new kinds of spreaders and fertilisers. © 2009 IAgrE.status: publishe