Unjamming and nematic flocks in endothelial monolayers during angiogenesis : theoretical and experimental analysis

TL;DR

This paper combines experimental and theoretical approaches to understand how VEGF influences cell jamming, unjamming, and nematic order in endothelial monolayers during angiogenesis, revealing mechanisms of cell flow and orientation.

Contribution

It introduces a mathematical model describing unjamming and nematic reorientation of endothelial cells, integrating continuum mechanics and active biopolymer theory.

Findings

VEGF induces a jamming/unjamming transition in endothelial monolayers.

Cell flow resembles evacuation processes with convergent channels.

The model predicts cell flow and orientation during early capillary formation.

Abstract

Angiogenesis is the complex process by which new blood vessels develop from an existing vasculature in order to supply nutrients and/or metabolites to tissues, playing a fundamental role in many physiological and pathological conditions such as embryogenesis and tissue repair or tumour growth. Here we analysed the \textit{in-vitro} angiogenic process from the perspective of the monolayer to understand the role of the interaction between the surrounding endothelial monolayer, the sprouting and the mechanics. First we noticed that the VEGF (Vascular Endothelial Growth Factor) promotes a jamming/unjamming transition that allows the fluidisation of the monolayer by measuring the shape index factor. Next, we measured the density field over the monolayer and realised that the flow of cells manifests strong similarities with the evacuation process where the flock of cells can flow or stuck, defining a convergent channel. Based on these novel observations we propose a mathematical model to describe the effects of unjamming and reorientation of a flock of cells which flow from the monolayer towards the early capillary structure. This model is developed into the framework of the continuum mechanics in which we consider the endothelial monolayer as an active biopolymer film where the nematic order emerges in the unjammed phase promoted by the VEGF activation. To test the proposed ideas we implement the developed coupled equations into a finite element code and describe, with a simplified geometry, the flow effect and cells orientation from the monolayer to the capillary. In this work, we propose an interpretation, from the top of the endothelial monolayer, based on experimental observations and theoretical arguments to think the angiogenesis.