Computational modelling of angiogenesis: The importance of cell rearrangements during vascular growth

Abstract

Angiogenesis is the process wherein endothelial cells (ECs) form sprouts that elongate from the pre-existing vasculature to create new vascular networks. In addition to its essential role in normal development, angiogenesis plays a vital role in pathologies such as cancer, diabetes and atherosclerosis. Mathematical and computational modelling has contributed to unravelling its complexity. Many existing theoretical models of angiogenic sprouting are based on the 'snail-trail' hypothesis. This framework assumes that leading ECs positioned at sprout tips migrate towards low-oxygen regions while other ECs in the sprout passively follow the leaders' trails and proliferate to maintain sprout integrity. However, experimental results indicate that, contrary to the snail-trail assumption, ECs exchange positions within developing vessels, and the elongation of sprouts is primarily driven by directed migration of ECs. The functional role of cell rearrangements remains unclear. This review of the theoretical modelling of angiogenesis is the first to focus on the phenomenon of cell mixing during early sprouting. We start by describing the biological processes that occur during early angiogenesis, such as phenotype specification, cell rearrangements and cell interactions with the microenvironment. Next, we provide an overview of various theoretical approaches that have been employed to model angiogenesis, with particular emphasis on recent in silico models that account for the phenomenon of cell mixing. Finally, we discuss when cell mixing should be incorporated into theoretical models and what essential modelling components such models should include in order to investigate its functional role.

arXiv comment27 pages, 9 figures, 1 table

References in corpus (9)

• Collective motion and nonequilibrium cluster formation in colonies of gliding bacteria
• Percolation, Morphogenesis, and Burgers Dynamics in Blood Vessels Formation
• Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth
• Mechanical cell-matrix feedback explains pairwise and collective endothelial cell behavior in vitro
• Vascular network remodeling via vessel cooption, regression and growth in tumors
• Bridging from single to collective cell migration: A review of models and links to experiments
• Mesoscopic and continuum modelling of angiogenesis
• Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis---a computational study
• Topological data analysis distinguishes parameter regimes in the Anderson-Chaplain model of angiogenesis