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.
Sprouting angiogenesis is a core biological process critical to vascular development. Its accurate simulation, relevant to multiple facets of human health, is of broad, interdisciplinary appeal. This study presents an in-silico model replicating a microfluidic assay where endothelial cells sprout into a biomimetic extracellular matrix, specifically, a large-pore, low-concentration fibrin-based porous hydrogel, influenced by chemotactic factors. We introduce a novel approach by incorporating the extracellular matrix and chemotactic factor effects into a unified term using a single parameter, primarily focusing on modelling sprouting dynamics and morphology. This continuous model naturally describes chemotactic-induced sprouting with no need for additional rules. In addition, we extended our base model to account for matrix sensing and degradation, crucial aspects of angiogenesis. We validate our model via a hybrid in-silico experimental method, comparing the model predictions with experimental results derived from the microfluidic setup. Our results underscore the intricate relationship between the extracellular matrix structure and angiogenic sprouting, proposing a promising method for predicting the influence of the extracellular matrix on angiogenesis.
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