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Cell-based, computational modeling of mechanical cell-matrix interactions during embryonic development Merks, Roeland

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During embryonic development, the behavior of individual cells must be coordinated to create the large scale patterns and tissue movements that shape the whole embryo. Apart from chemical signaling, it has recently become clear that mechanical cell-cell communication is equally important in the coordination of such collective cell behavior. To get a better understanding of mechanical cell-cell communication, we are developing computational models of cells and the extracellular matrix (ECM) - the hard or jelly materials (e.g. collagens, fibronectin) that form the micro-environment of many cells. The models are detailed enough for explaining the response of individual cells to the mechanical properties of the ECM, and sufficiently coarse-grained so as to allow for efficient computational upscaling to the tissue level and beyond. Our model is based on a novel, hybrid Cellular Potts and finite element computational framework. It describes the contractile forces that cells exert on the ECM, the resulting strain fields in the ECM, and the cellular response to local strains. The model simulations reproduce the behavior of individual endothelial cells on compliant matrices, and show that local cell-ECM interactions suffice for explaining interactions of endothelial cell pairs and collective cell behavior, including the formation of cellular networks and sprouting from spheroids [1]. If an external strain is exerted on the ECM, the cells rapidly align with the strain fields, even in response to very subtle strain cues [2]. These initial models relied on phenomenological descriptions of the interactions between cellular protrusions and the ECM. Recently, detailed measurements and new mathematical models of the kinetics of individual focal adhesions (the macromolecular assemblies responsible for mechanical cell-ECM interactions) have become available. In our ongoing work we have include kinetic descriptions of focal adhesions in our models. We will sketch how this approach will allow us to mechanistically predict changes in cell shape and in collective cell behavior from changes in focal adhesion kinetics. Altogether, our models suggest simple mechanisms by which local, mechanical cell-ECM interactions can assist in integrating morphological information in embryos across organizational levels.
[1] R. F. M. van Oers, E. G. Rens, D. J. LaValley, C. A. Reinhart-King, and R. M. H. Merks, “Mechanical Cell-Matrix Feedback Explains Pairwise and Collective Endothelial Cell Behavior In Vitro,” PLoS Comput. Biol., vol. 10, no. 8, p. e1003774, Aug. 2014.
[2] E. G. Rens and R. M. H. Merks, “Cell Contractility Facilitates Alignment of Cells and Tissues to Static Uniaxial Stretch,” Biophysical Journal, vol. 112, no. 4, pp. 755–766, Feb. 2017.

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