Technologies. University of Tehran Flow-induced effect of matrix fiber orientation on endothelial vasculogenesis

Topography of extracellular matrix plays a major role in many biological events including tissue healing, morphogenesis and growth. It is known that matrix constitution and mechanical properties are deciding factors in governing the fate of its inhabitant cells. Besides the direct mechanical cues, matrices also facilitate the release and uptake of certain chemicals and participate in cell-cell and cell- ECM crosstalk. Mechanical strains in the matrix are proved to direct endothelial cell migration and elongation leading to angiogenesis, and there is a consensus that matrix stiffness, fiber density and fiber orientation can enhance angiogenesis in the preferred direction of stiffness gradient. In this study, we specifically investigated the role of topography in guidance of endothelial self-reorganization prompted by the effect of fluid flow hindrance and facilitation in certain directions. We adopted our previous model of fluid flow guided angiogenesis for cellular responses. Lattice Boltzmann model of fluid flow was adopted and modified to study the effect of unidirectional and randomly oriented fibers. To study the effect of fiber orientation, we customized a previously proposed model of porosity in lattice Boltzmann to suit this purpose. This model could reproduce the effects of fiber orientations in matrix on endothelial migration and vasculogenesis. Simulations showed better confluency of formed lumens when prescribed flow is in the direction of fiber orientation. These results can have further implications in understanding endothelial complications in certain diseases as well as in tumor angiogenesis and metastasis.