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

TL;DR

This paper reviews computational models of angiogenesis, emphasizing the importance of cell rearrangements and mixing during early vascular sprouting, challenging traditional 'snail-trail' assumptions and highlighting recent in silico approaches.

Contribution

It is the first review to focus specifically on cell mixing phenomena in angiogenesis models and discusses how to incorporate this into theoretical frameworks.

Findings

Cell rearrangements are crucial in early angiogenic sprouting.

Recent models incorporate cell mixing to better reflect biological processes.

Understanding cell dynamics can improve predictions of 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.