Inall sciences, models are used to represent, usually in an simplified form, amore complex and detailed reality. Models and simulations are used because insome way, they are more accessible, convenient, or familiar to practitionersthan the in vivo experiments. They represent more explicitly the state of knowledge, predict results, oract as the objects of further experiments. Most importantly, a model is arepresentation of some reality that embodies some essential and interestingaspects of that reality, but not all of it.
Creatinga cellular model has been a particularly challenging task of systems in biologyand mathematical biology . Through this kind of models is easier to analyze andvisualize the complex connections of these cellular processes. It involves theuse of computer simulations environment that allows rapid and intuitivemodeling and simulation of cellular and multicellular behaviors in the contextof tissue formation .
Collectivecell migration describes the movements of group of cells and the emergence ofcollective behavior from cell-environment interactions and cell-cellcommunication.1 Collective cell migration is an essential process inthe lives of multicellular organisms. Cells can migrate as a cohesive group(e.g. epithelial cells) or have transient cell-cell adhesion sites (e.g.mesenchymal cells).They can also migrate in different modes like sheets,strands, tubes, and clusters.
While single-cell migration has been extensivelystudied, collective cell migration is a relatively new field with applications.Invitro studies have shown that cells become more prone to collective migrationwhen they are confined onto micropatterned surfaces. To study this in vivo,scientists mainly focus on neural crest cells migration and they experimentallycame up with results that NCC migration in vivo is enhanced by spatialconfinement. The confining factor plays a contradictory role acting as aninhibitor of migration to form exclusionary boundaries and, at the same time,required for collective migration of NCCs. In particular this confining factoris about to be the versican. 1,2Thisconfinement forms an inhibitory boundary around NC streams and the loss of versican in vivo leads to altered NC migration and directionallycollective movement of the cells in silico without affecting cell motility.Also it is essential the width of the confinement and the size of the cellcluster for the efficiency of the migration.
Furthermore, studying thewidespread biological phenomenon of cell migration, it was observed ,that uponexposure to chemokine gradients (CCL19 or CXCL12) lymphocytes assembled intoclusters that migrate directionally and display a wider chemotactic sensitivitythan individual cells. Single cells undergo chemorepulsion when exposed to highdoses of chemokine and collective lymphoid cells are stack together throughadhesive receptors that are critical to establish the differential polarity ofindividual cells within the clusters and for collective directional migration. Theanalysis and the understanding of the behavior of the single cells in contrastto clusters, as they move up to a chemoattractant gradient, leads to considerall the significant factors that influence this procedure.
Specifically ,parameters like temperature , positive and negative chemotaxis ?, the boundaryvalue that determines the polarizing from a cell type to another seem to affectthe evolution of the process and the differences between the collective orindividual cell performance. METHODSMulti-cellcomputer simulation methods, ranging from relatively simple cellular automatato complex immersed-boundary models, allow in silico study of multi-cellphenomena at the tissue scale based on biologically observed cell behaviors andinteractions such as movement, adhesion, growth,secretion of chemicals,chemotaxis, etc. CompuCell3D simulation environment allows rapid and intuitivemodeling and simulation of cellular and multi-cellular behaviors in the contextof tissue formation and subsequent dynamics.
This way models are useful in both suggesting hypotheses and testing them. CC3D allows users to build sophisticatedmodels more easily and quickly than specialized custom code. A CC3D modelconsists of CC3DML scripts (an XML-based format), Python scripts, and files specifyingthe initial configurations of the cell lattice. The CC3DML script specifiesbasic GGH (Glazier-Graner-Hogeweg) parameters such as lattice dimensions, celltypes, biological mechanisms.
Pythonscripts primarily monitor the state of the simulation and implement changes incell behaviors.3Themodel that we built using CompuCell3D is meant to get an insight into thebehaviour of single and cluster cells under the influence of a chemical field. Inthe model we imposed two different type of cells: the attract-cell and therepel-cell. The attract-cell is attracted to the gradient and the repel-cell isrepulsed. At the beginning of the simulation we had an attract-cell. As thegradient got steeper this cell flipped to a repel-cell and on the other side asthe gradient got smoother the repel-cell changed to an attract-cell .
Tocompare the differences in the behaviourof the cells we used three different cluster sizes. At first we did the simulations for 1 cell , afterwardsfor one small cluster of cells ( 9 cells) and finally for a bigger cluster (21cells). In every simulation after varying one parameter (chemotaxis ?, flipping values, temperature) ofthe model and analyzing the observationswe could see what influence the variable had on the system.
