MODELLING THE INFLUENCE OF NUCLEUS ELASTICITY ON CELL INVASION IN FIBER NETWORKS

Cell migration in highly constrained extracellular matrices is exploited in scaffold-based tissue engineering and is fundamental in a wide variety of physiological and pathological phenomena, among other in cancer invasion and development. Research into the critical processes involved in cell migration has mainly focused on cell adhesion and proteolytic degradation of the external environment. However, arising evidence has recently shown that a number of cell-derived biophysical and mechanical parameters, among others nucleus stiffness and cell deformability, plays a major role in cell motility, especially in the ameboid-like migration mode in 3D confined tissue structures. We here present an extended Cellular Potts Model (CPM) first used to simulate a microfabricated migration chip, which tests the active invasive behavior of cancer cells into narrow channels. As distinct features of our approach, cells are modeled as compartmentalized discrete objects, differentiated in the nucleus and in the cytosolic region, while the migration chamber is composed of channels of different widths. We find that cell motile phenotype and velocity in open spaces (i.e., 2D flat surfaces or large channels) is not significantly influenced by cell elastic properties. On the contrary, the migratory behavior of cells within subcellular and subnuclear structures strongly relies on the deformability of the cytosol and and the nuclear cluster, respectively. Further, we characterize two migration dynamics: a stepwise way, characterized by fluctuations in cell length, within channels smaller than nucleus dimensions and a smooth sliding (i.e., maintaining constant cell length) behavior within channels larger than the nuclear cluster. These resulting observations are then extended looking at cell migration in an artificial fiber network, which mimics cell invasion in a 3D extracellular matrix. In particular, in this case, we analyze the effect on cell movement of variations in elasticity of the nucleus. In order to summarize, with our simulated migration assays, we demonstrate that the dimensionality of the environment strongly affects the migration phenotype and we suggest that the cytoskeletal and nuclear elastic characteristics correlate with the tumor cells invasive potential. keywords: cellular potts model · extracellular matrix · cell migration · microchannels 1Corresponding Author. E-Mail: marcosci1@alice.it 2Corresponding Author. E-Mail: luigi.preziosi@polito.it 1 Politecnico di Torino M. Scianna and L. Preziosi Cell Invasion in Fiber Networks and Microchannels

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