An in silico study on the influence of extracellular matrix mechanics on vasculogenesis

Abstract

Background and objectives: Blood vessels form a network of capillaries throughout the body that perform essential functions for life. Vasculogenesis, i.e. the formation of new blood vessels, is regulated by many factors, biochemical ones being among the most important. However, others such as the biomechanical influence on shape, organization and structure of vessel networks require further investigation. In this paper, we develop a 3D agent-based mechanobiological model of vasculogenesis with the aim of analyzing how the mechanics of the extracellular matrix (ECM) affects vasculogenesis. Methods: For this purpose, we consider a growing domain composed of different cells: tip cells, which are the driving cells located at the end of the vessels and stalk cells, which are found in the interior of the vascular network. ECM is considered as particles (agents) that surround the growth of the vascular network. Depending on the cell type, different sets of forces are considered, such as chemotactic, mechanical, random and viscoelastic forces among others. Results: The growth of the network is iteratively analyzed and updated at each time step based on a mechanically-driven proliferation rule. The influence of different biomechanical factors, such as ECM stiffness or viscoelasticity are explored through in silico simulations. A number of indicators are defined along the algorithm, like number of cells, branches, tortuosity and anisotropy, in order to compare topological differences of the vascular network during vasculogenesis under different ECM conditions. The obtained results are qualitatively compared with other related works in the literature. Conclusions: The present study sheds some light and partially explain, from an in silico perspective, the role of ECM mechanics on vasculogenesis. The main conclusions of this work are: (i) increased stiffness increases proliferation, (ii) the network tends to migrate towards stiffer areas, and (iii) increased viscoelasticity decreases proliferation.