Mathematical investigation of normal and abnormal wound healing dynamics:local and non-local model

The movement of cells during (normal and abnormal) wound healing is the result of biomechanical interactions that combine cell responses with growth factors as well as cell-cell and cell-matrix interactions (adhesion and remodelling). It is known that cells can communicate and interact locally and non-locally with other cells inside the tissues through mechanical forces that act locally and at a distance, as well as through long non-conventional cell protrusions. In this study, we consider a non-local partial differential equation model for the interactions between fibroblasts, macrophages and the extracellular matrix (ECM) via a growth factor (TGF-β) in the context of wound healing. For the non-local interactions, we consider two types of kernels (i.e., a Gaussian kernel and a cone-shaped kernel), two types of cell-ECM adhesion functions (i.e., adhesion only to higher-density ECM vs. adhesion to higher-/lower-density ECM) and two types of cell proliferation terms (i.e., with and without decay due to overcrowding). We investigate numerically the dynamics of this non-local model, as well as the dynamics of the localised versions of this model (i.e., those obtained when the cell perception radius decreases to 0). The results suggest the following: (i) local models explain normal wound healing and non-local models could also explain abnormal wound healing (although the results are parameter-dependent); (ii) the models can explain two types of wound healing, i.e., by primary intention, when the wound margins come together from the side, and by secondary intention when the wound heals from the bottom up.</p

Non-local kinetic and macroscopic models for self-organised animal aggregations

The last two decades have seen a surge in kinetic and macroscopic models derived to investigate the multi-scale aspects of self-organised biological aggregations. Because the individual-level details incorporated into the kinetic models (e.g., individual speeds and turning rates) make them somewhat difficult to investigate, one is interested in transforming these models into simpler macroscopic models, by using various scaling techniques that are imposed by the biological assumptions of the models. However, not many studies investigate how the dynamics of the initial models are preserved via these scalings. Here, we consider two scaling approaches (parabolic and grazing collision limits) that can be used to reduce a class of non-local 1D and 2D models for biological aggregations to simpler models existent in the literature. Then, we investigate how some of the spatio-temporal patterns exhibited by the original kinetic models are preserved via these scalings. To this end, we focus on the parabolic scaling for non-local 1D models and apply asymptotic preserving numerical methods, which allow us to analyse changes in the patterns as the scaling coefficient ϵ is varied from ϵ=1 (for 1D transport models) to ϵ=0 (for 1D parabolic models). We show that some patterns (describing stationary aggregations) are preserved in the limit ϵ→0, while other patterns (describing moving aggregations) are lost. To understand the loss of these patterns, we construct bifurcation diagrams

Modelling Stochastic and Deterministic Behaviours in Virus Infection Dynamics

Many human infections with viruses such as human immunodeficiency virus type 1 (HIV--1) are characterized by low numbers of founder viruses for which the random effects and discrete nature of populations have a strong effect on the dynamics, e.g., extinction versus spread. It remains to be established whether HIV transmission is a stochastic process on the whole. In this study, we consider the simplest (so-called, 'consensus') virus dynamics model and develop a computational methodology for building an equivalent stochastic model based on Markov Chain accounting for random interactions between the components. The model is used to study the evolution of the probability densities for the virus and target cell populations. It predicts the probability of infection spread as a function of the number of the transmitted viruses. A hybrid algorithm is suggested to compute efficiently the dynamics in state space domain characterized by a mix of small and large species densities

Mathematical models for immunology:current state of the art and future research directions

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years

What is the in-host dynamics of SARS-CoV-2 virus? A challenge within a multiscale vision of living systems

This paper deals with the modeling and simulation of the in-host dynamics of a virus. The modeling approach is developed according to the idea that mathematical models should go beyond deterministic single-scale population dynamics by taking into account the multiscale, heterogeneous features of the complex system under consideration. Here we consider modeling the competition between the virus, the epithelial cells it infects, and the heterogeneous immune system with evolving activation states that induce a range of different effects on virus particles and infected cells. The subsequent numerical simulations show different types of model outcomes: from virus elimination, to virus persistance and periodic relapse, and virus uncontrolled growth that triggers a blow-up in the fully-activated immune response. The simulations also show the existence of a threshold in the immune response that separates the regimes of higher re-infections from lower re-infections (compared to the magnitude of the first viral infection)