A mathematical model for chemotactic endothelial cell migration through a fibrin-based extracellular matrix

Abstract

Migration is a fundamental cellular behaviour that plays an essential role in vascular development and angiogenesis. Due to its relevance to many aspects of human health, the ability to accurately reproduce cell migration is of broad and multidisciplinary interest. This work presents a model to reproduce a microfluidic assay in which endothelial cells chemotactically migrate into a fibrin-based porous hydrogel. Endothelial cells emanate from a parent vessel through the extracellular matrix towards the increasing chemotactic factor concentration. We couple into the same parameter the extracellular matrix and the chemotactic factor distribution. We focus our efforts on modelling sprouting dynamics and morphology, providing a new framework to understand cell migration and the influence of the extracellular matrix. The model naturally describes chemotactic cell behaviour in response to the extracellular matrix structure. We further extend our model to allow extracellular matrix sensing and degradation. We validated the model based on a hybrid in silico-experimental approach by comparing it against the experimental results obtained in the microfluidic assay. Together, our findings highlight the nontrivial role of the extracellular matrix structure in angiogenic sprouting and offer an approach to predicting the effect of the extracellular matrix.