Modeling hypoxia-related inflammation scenarios.

Cells respond to hypoxia via the activation of three isoforms of Hypoxia Inducible Factors (HIFs), that are characterized by different activation times. HIF overexpression has many effects on cell behavior, such as change in metabolism, promotion of angiogenic processes and elicitation of a pro-inflammatory response. These effects are driving forces of malignant progression in cancer cells. In this work we study in detail hypoxia-induced dynamics of HIF1α and HIF2α, which are the most studied isoforms, comparing available experimental data on their evolution in tumor cells with the results obtained integrating the deduced mathematical model. Then, we examine the possible scenarios that characterize the link between hypoxia and inflammation via the activation of NFkB (Nuclear Factor k-light-chain-enhancer of activated B cells) when the dimensionless groups of parameters of the mathematical model change. In this way we are able to discuss why and when hypoxic conditions lead to acute or chronic inflammatory states.

Modelling chase-and-run migration in heterogeneous populations.

Cell migration is crucial for many physiological and pathological processes. During embryogenesis, neural crest cells undergo coordinated epithelial to mesenchymal transformations and migrate towards various forming organs. Here we develop a computational model to understand how mutual interactions between migrating neural crest cells (NCs) and the surrounding population of placode cells (PCs) generate coordinated migration. According to experimental findings, we implement a minimal set of hypotheses, based on a coupling between chemotactic movement of NCs in response to a placode-secreted chemoattractant (Sdf1) and repulsion induced from contact inhibition of locomotion (CIL), triggered by heterotypic NC-PC contacts. This basic set of assumptions is able to semi-quantitatively recapitulate experimental observations of the characteristic multispecies phenomenon of "chase-and-run", where the colony of NCs chases an evasive PC aggregate. The model further reproduces a number of in vitro manipulations, including full or partial disruption of NC chemotactic migration and selected mechanisms coordinating the CIL phenomenon. Finally, we provide various predictions based on altering other key components of the model mechanisms.

Modelling human perception processes in pedestrian dynamics: a hybrid approach.

In this paper, we present a hybrid mathematical model describing crowd dynamics. More specifically, our approach is based on the well-established Helbing-like discrete model, where each pedestrian is individually represented as a dimensionless point and set to move in order to reach a target destination, with deviations deriving from both physical and social forces. In particular, physical forces account for interpersonal collisions, whereas social components include the individual desire to remain sufficiently far from other walkers (the so-called territorial effect). In this respect, the repulsive behaviour of pedestrians is here set to be different from traditional Helbing-like methods, as it is assumed to be largely determined by how they perceive the presence and the position of neighbouring individuals, i.e. either objectively as pointwise/localized entities or subjectively as spatially distributed masses. The resulting modelling environment is then applied to specific scenarios, that first reproduce a real-world experiment, specifically designed to derive our model hypothesis. Sets of numerical realizations are also run to analyse in more details the pedestrian paths resulting from different types of perception of small groups of static individuals. Finally, analytical investigations formalize and validate from a mathematical point of view selected simulation outcomes.

Coherent modelling switch between pointwise and distributed representations of cell aggregates.

Biological systems are typically formed by different cell phenotypes, characterized by specific biophysical properties and behaviors. Moreover, cells are able to undergo differentiation or phenotypic transitions upon internal or external stimuli. In order to take these phenomena into account, we here propose a modelling framework in which cells can be described either as pointwise/concentrated particles or as distributed masses, according to their biological determinants. A set of suitable rules then defines a coherent procedure to switch between the two mathematical representations. The theoretical environment describing cell transition is then enriched by including cell migratory dynamics and duplication/apoptotic processes, as well as the kinetics of selected diffusing chemicals influencing the system evolution. Finally, biologically relevant numerical realizations are presented: in particular, they deal with the growth of a tumor spheroid and with the initial differentiation stages of the formation of the zebrafish posterior lateral line. Both phenomena mainly rely on cell phenotypic transition and differentiated behaviour, thereby constituting biological systems particularly suitable to assess the advantages of the proposed model.

A Cellular Potts Model of single cell migration in presence of durotaxis.

Cell migration is a fundamental biological phenomenon during which cells sense their surroundings and respond to different types of signals. In presence of durotaxis, cells preferentially crawl from soft to stiff substrates by reorganizing their cytoskeleton from an isotropic to an anisotropic distribution of actin filaments. In the present paper, we propose a Cellular Potts Model to simulate single cell migration over flat substrates with variable stiffness. We have tested five configurations: (i) a substrate including a soft and a stiff region, (ii) a soft substrate including two parallel stiff stripes, (iii) a substrate made of successive stripes with increasing stiffness to create a gradient and (iv) a stiff substrate with four embedded soft squares. For each simulation, we have evaluated the morphology of the cell, the distance covered, the spreading area and the migration speed. We have then compared the numerical results to specific experimental observations showing a consistent agreement.

A review of mathematical models for the formation of vascular networks.

Two major mechanisms are involved in the formation of blood vasculature: vasculogenesis and angiogenesis. The former term describes the formation of a capillary-like network from either a dispersed or a monolayered population of endothelial cells, reproducible also in vitro by specific experimental assays. The latter term describes the sprouting of new vessels from an existing capillary or post-capillary venule. Similar mechanisms are also involved in the formation of the lymphatic system through a process generally called lymphangiogenesis. A number of mathematical approaches have been used to analyze these phenomena. In this paper, we review the different types of models, with special emphasis on their ability to reproduce different biological systems and to predict measurable quantities which describe the overall processes. Finally, we highlight the advantages specific to each of the different modelling approaches.