A Model of Integrin and VEGF Receptors Recruitment on Endothelial Cells

Abstract

Angiogenesis is a multistep process in which endothelial cells (ECs) are affected by several extracellular stimuli, including growth factors, extracellular matrix (ECM), and parenchymal and stromal cells. In this process, growth factor receptors as well as adhesion receptors convey the extracellular signaling in a coordinate intracellular pathway. The Vascular Endothelial Growth Factor (VEGF), by binding the Vascular endothelial growth factor receptor 2 (VEGFR-2), promotes EC proliferation, migration, and their reorganization in active vessels. Once engaged, the activation of VEGFR-2 is modulated by its interaction with β₃ integrin. Although the ability of VEGFR-2 to participate in a complex with β₃ integrin is well known, the close correlation between their activation and the multiphysical phenomena regulating EC dynamics remains still very restricted. Here we computationally model the VEGFR-2 and β₃ integrin membrane dynamics by a multi-physics model, to identify how ligands stimulation induces the polarization of receptors in cell protrusions and in the basal aspect of ECs plated on a ligand-enriched ECM. The research for new anti-angiogenic solutions through the controlled activation of the ECs could arise from the determination of the laws that govern the polarization of the receptors.