A cellular Potts model analyzing differentiated cell behavior during in vivo vascularization of a hypoxic tissue

Abstract

Angiogenesis, the formation of new blood vessel networks from existing capillary or post-capillary venules, is an intrinsically multiscale process occurring in several physio-pathological conditions. In particular, hypoxic tissue cells activate downstream cascades culminating in the secretion of a wide range of angiogenic factors, including VEGF isoforms. Such diffusive chemicals activate the endothelial cells (ECs) forming the external walls of the nearby vessels, that chemotactictally migrate toward the hypoxic areas of the tissue as multicellular sprouts. A functional network eventually emerges by further branching and anastomosis processes. We here propose a CPM-based approach reproducing selected features of the angiogenic progression necessary for the reoxygenation of a hypoxic tissue. Our model is able to span the different scale involved in the angiogenic progression as it incorporates reaction-diffusion equations for the description of the evolution of microenvironmental variables in a discrete mesoscopic cellular Potts model (CPM) that reproduces the dynamics of the vascular cells. A key feature of this work is the explicit phenotypic differentiation of the ECs themselves, distin-1 E-Mail: marcosci1@alice.it 2 E-Mail: eleonora.bassino@unito.it 3 E-Mail: luca.munaron@unito.it Preprint submitted to Computers in Biology and Medicine May 25, 2015 guished in quiescent, stalk and tip. The simulation results allow identifying a set of key mechanisms underlying tissue vascularization. Further, we provide evidence that the nascent pattern is characterized by precise topological properties. Finally, we link abnormal sprouting angiogenesis with alteration in selected cell behavior.

An Innovative Assay for the Analysis of In Vitro Endothelial Remodeling: Experimental and Computational Evidence

“…The increment in the intercellular adhesive interactions (consequent to the higher cell density) partially disrupts the regulation of the chemotactic component of cell migration, which is required for a proper networking behavior. This mechanism, called 'contact inhibition of chemotaxis', has been widely recognized and described in the experimental and computational literature (Hellstrom et al, 2007;Lin et al, 2015;Scianna et al, 2015).…”

Multiscale modeling methods in biomechanics

“…Using a cellular Potts modeling framework, Scianna et al . investigated angiogenesis by detailing the interactions between cellular and molecular scale models, and investigated vasculogenesis by detailing the interactions between subcellular, cellular and extracellular scale models. The multiscale models parameters in each study were determined from experimental evidence in literature, and model prediction qualitatively agreed with observed characteristics.…”

“…Scianna et al . incorporated the influence of vascular endothelial growth factor (VEGF) on cellular signaling by defining a model of VEGF diffusion at the extracellular scale and models simulating subcellular processes in dependence of VEGF concentration.…”

UPMaBoSS: a novel framework for dynamic cell population modeling

“…All these di↵erent methodologies have their own applications, e.g. CellSys, PhysiCell and PhysiBoSS for tumor growth, Epilog for spatial patterning, Potts models for vascularisation and angiogenesis [19], and are very promising to explore the e↵ects of perturbations at the level of individual cells and understand how these perturbations impact cell populations. They constitute a first step towards the use of multi-scale modeling for clinical applications [20,21].…”