Angiogenesis, the new blood vessel formation from a pre-existing one, is an essential process of cancer growth. Many proteins play major roles in this phenomenon and we focus to the interactions among receptors, in particular Vascular Endothelial Growth Factors Receptor 2 (VEGFR-2), and their canonical and non canonical ligands, as Vascular Endothelial Growth Factors (VEGF) and Gremlin,ontheendothelialcell(EC)membrane. LigandbindingtoVEGFR-2isassociatedwiththe receptordimerizationandactivation,whichtriggersadownstreamsignalingpathwaysleadingtoEC proliferation. The complex VEGFR-2/ligand interacts with others transmembrane receptors, which includes αvβ3 integrins [1], responsible of cell contractility, and co-receptors, as neuropilin (NRP). Mathematical models and computer simulations, accounting for the many findings that have been provided by biologists, are able to predict conditions for angiogenesis and to identify new strategies in drug delivery. Co-designedexperimentsandsimulationsforVEGFR-2relocalizationdrivenbyVEGForGremlin has been recently proposed by the authors [2]. The model is based on continuity equations (for mass, energy and entropy), standard chemical kinetics, thermodynamics restrictions, and constitutive specifications. The governing equations in a weak form, are approximated by Finite Element andBackwardEulerMethodsandimplementedinain-housecomputercode. Numericalsimulations have been validated against experimental data.
Simulation of VEGF receptor recruitment on ECs membrane
Valentina Damioli;Alberto Salvadori;Mattia Serpelloni;Gian Paolo Beretta;Cosetta Ravelli;Stefania Mitola
2018-01-01
Abstract
Angiogenesis, the new blood vessel formation from a pre-existing one, is an essential process of cancer growth. Many proteins play major roles in this phenomenon and we focus to the interactions among receptors, in particular Vascular Endothelial Growth Factors Receptor 2 (VEGFR-2), and their canonical and non canonical ligands, as Vascular Endothelial Growth Factors (VEGF) and Gremlin,ontheendothelialcell(EC)membrane. LigandbindingtoVEGFR-2isassociatedwiththe receptordimerizationandactivation,whichtriggersadownstreamsignalingpathwaysleadingtoEC proliferation. The complex VEGFR-2/ligand interacts with others transmembrane receptors, which includes αvβ3 integrins [1], responsible of cell contractility, and co-receptors, as neuropilin (NRP). Mathematical models and computer simulations, accounting for the many findings that have been provided by biologists, are able to predict conditions for angiogenesis and to identify new strategies in drug delivery. Co-designedexperimentsandsimulationsforVEGFR-2relocalizationdrivenbyVEGForGremlin has been recently proposed by the authors [2]. The model is based on continuity equations (for mass, energy and entropy), standard chemical kinetics, thermodynamics restrictions, and constitutive specifications. The governing equations in a weak form, are approximated by Finite Element andBackwardEulerMethodsandimplementedinain-housecomputercode. Numericalsimulations have been validated against experimental data.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
