Modelling microtube driven invasion of glioma.

Malignant gliomas are notoriously invasive, a major impediment against their successful treatment. This invasive growth has motivated the use of predictive partial differential equation models, formulated at varying levels of detail, and including (i) "proliferation-infiltration" models, (ii) "go-or-grow" models, and (iii) anisotropic diffusion models. Often, these models use macroscopic observations of a diffuse tumour interface to motivate a phenomenological description of invasion, rather than performing a detailed and mechanistic modelling of glioma cell invasion processes. Here we close this gap. Based on experiments that support an important role played by long cellular protrusions, termed tumour microtubes, we formulate a new model for microtube-driven glioma invasion. In particular, we model a population of tumour cells that extend tissue-infiltrating microtubes. Mitosis leads to new nuclei that migrate along the microtubes and settle elsewhere. A combination of steady state analysis and numerical simulation is employed to show that the model can predict an expanding tumour, with travelling wave solutions led by microtube dynamics. A sequence of scaling arguments allows us reduce the detailed model into simpler formulations, including models falling into each of the general classes (i), (ii), and (iii) above. This analysis allows us to clearly identify the assumptions under which these various models can be a posteriori justified in the context of microtube-driven glioma invasion. Numerical simulations are used to compare the various model classes and we discuss their advantages and disadvantages.

Cell orientation under stretch: A review of experimental findings and mathematical modelling.

The key role of electro-chemical signals in cellular processes had been known for many years, but more recently the interplay with mechanics has been put in evidence and attracted substantial research interests. Indeed, the sensitivity of cells to mechanical stimuli coming from the microenvironment turns out to be relevant in many biological and physiological circumstances. In particular, experimental evidence demonstrated that cells on elastic planar substrates undergoing periodic stretches, mimicking native cyclic strains in the tissue where they reside, actively reorient their cytoskeletal stress fibres. At the end of the realignment process, the cell axis forms a certain angle with the main stretching direction. Due to the importance of a deeper understanding of mechanotransduction, such a phenomenon was studied both from the experimental and the mathematical modelling point of view. The aim of this review is to collect and discuss both the experimental results on cell reorientation and the fundamental features of the mathematical models that have been proposed in the literature.

An SIR model with viral load-dependent transmission.

The viral load is known to be a chief predictor of the risk of transmission of infectious diseases. In this work, we investigate the role of the individuals' viral load in the disease transmission by proposing a new susceptible-infectious-recovered epidemic model for the densities and mean viral loads of each compartment. To this aim, we formally derive the compartmental model from an appropriate microscopic one. Firstly, we consider a multi-agent system in which individuals are identified by the epidemiological compartment to which they belong and by their viral load. Microscopic rules describe both the switch of compartment and the evolution of the viral load. In particular, in the binary interactions between susceptible and infectious individuals, the probability for the susceptible individual to get infected depends on the viral load of the infectious individual. Then, we implement the prescribed microscopic dynamics in appropriate kinetic equations, from which the macroscopic equations for the densities and viral load momentum of the compartments are eventually derived. In the macroscopic model, the rate of disease transmission turns out to be a function of the mean viral load of the infectious population. We analytically and numerically investigate the case that the transmission rate linearly depends on the viral load, which is compared to the classical case of constant transmission rate. A qualitative analysis is performed based on stability and bifurcation theory. Finally, numerical investigations concerning the model reproduction number and the epidemic dynamics are presented.

Intransigent vs. volatile opinions in a kinetic epidemic model with imitation game dynamics.

In the mathematical epidemiology community, there is an increasing interest in shaping the complex interplay between human behaviour and disease spreading. We give a contribution in this direction by illustrating a method to derive behavioural change epidemic models from a stochastic particle description by the means of kinetic equations. We consider a susceptible-infected-removed-like model where contact rates depend on the behavioural patterns adopted across the population. The selection of the social behaviour happens during the interactions between individuals adopting alternative strategies and it is driven by an imitation game dynamics. Agents have a double microscopic state: a discrete label, which denotes the epidemiological compartment to which they belong, and the degree of flexibility of opinion, i.e. a measure of the personal attitude to change opinion and, hence, to switch between the alternative social contact patterns. We derive kinetic evolution equations for the distribution functions of the degree of flexibility of opinion of the individuals for each compartment, whence we obtain macroscopic equations for the densities and average flexibilities of opinion. After providing the basic properties of the macroscopic model, we numerically investigate it by focusing on the impact of the flexibility of opinion on the epidemic course and on the consequent behavioural responses.

Opinion polarization in social networks.

In this paper, we propose a Boltzmann-type kinetic description of opinion formation on social networks, which takes into account a general connectivity distribution of the individuals. We consider opinion exchange processes inspired by the Sznajd model and related simplifications but we do not assume that individuals interact on a regular lattice. Instead, we describe the structure of the social network statistically, assuming that the number of contacts of a given individual determines the probability that their opinion reaches and influences the opinion of another individual. From the kinetic description of the system, we study the evolution of the mean opinion, whence we find precise analytical conditions under which a polarization switch of the opinions, i.e. a change of sign between the initial and the asymptotic mean opinions, occurs. In particular, we show that a non-zero correlation between the initial opinions and the connectivity of the individuals is necessary to observe polarization switch. Finally, we validate our analytical results through Monte Carlo simulations of the stochastic opinion exchange processes on the social network. This article is part of the theme issue 'Kinetic exchange models of societies and economies'.

Multi-Cue Kinetic Model with Non-Local Sensing for Cell Migration on a Fiber Network with Chemotaxis.

Cells perform directed motion in response to external stimuli that they detect by sensing the environment with their membrane protrusions. Precisely, several biochemical and biophysical cues give rise to tactic migration in the direction of their specific targets. Thus, this defines a multi-cue environment in which cells have to sort and combine different, and potentially competitive, stimuli. We propose a non-local kinetic model for cell migration in which cell polarization is influenced simultaneously by two external factors: contact guidance and chemotaxis. We propose two different sensing strategies, and we analyze the two resulting transport kinetic models by recovering the appropriate macroscopic limit in different regimes, in order to observe how the cell size, with respect to the variation of both external fields, influences the overall behavior. This analysis shows the importance of dealing with hyperbolic models, rather than drift-diffusion ones. Moreover, we numerically integrate the kinetic transport equations in a two-dimensional setting in order to investigate qualitatively various scenarios. Finally, we show how our setting is able to reproduce some experimental results concerning the influence of topographical and chemical cues in directing cell motility.

A viral load-based model for epidemic spread on spatial networks.

In this paper, we propose a Boltzmann-type kinetic model of the spreading of an infectious disease on a network. The latter describes the connections among countries, cities or districts depending on the spatial scale of interest. The disease transmission is represented in terms of the viral load of the individuals and is mediated by social contacts among them, taking into account their displacements across the nodes of the network. We formally derive the hydrodynamic equations for the density and the mean viral load of the individuals on the network and we analyse the large-time trends of these quantities with special emphasis on the cases of blow-up or eradication of the infection. By means of numerical tests, we also investigate the impact of confinement measures, such as quarantine or localised lockdown, on the diffusion of the disease on the network.

Stability of a non-local kinetic model for cell migration with density-dependent speed.

The aim of this article is to study the stability of a non-local kinetic model proposed by Loy & Preziosi (2020a) in which the cell speed is affected by the cell population density non-locally measured and weighted according to a sensing kernel in the direction of polarization and motion. We perform the analysis in a $d$-dimensional setting. We study the dispersion relation in the one-dimensional case and we show that the stability depends on two dimensionless parameters: the first one represents the stiffness of the system related to the cell turning rate, to the mean speed at equilibrium and to the sensing radius, while the second one relates to the derivative of the mean speed with respect to the density evaluated at the equilibrium. It is proved that for Dirac delta sensing kernels centered at a finite distance, corresponding to sensing limited to a given distance from the cell center, the homogeneous configuration is linearly unstable to short waves. On the other hand, for a uniform sensing kernel, corresponding to uniformly weighting the information collected up to a given distance, the most unstable wavelength is identified and consistently matches the numerical solution of the kinetic equation.

Modelling physical limits of migration by a kinetic model with non-local sensing.

Migrating cells choose their preferential direction of motion in response to different signals and stimuli sensed by spanning their external environment. However, the presence of dense fibrous regions, lack of proper substrate, and cell overcrowding may hamper cells from moving in certain directions or even from sensing beyond regions that practically act like physical barriers. We extend the non-local kinetic model proposed by Loy and Preziosi (J Math Biol, 80, 373-421, 2020) to include situations in which the sensing radius is not constant, but depends on position, sensing direction and time as the behaviour of the cell might be determined on the basis of information collected before reaching physically limiting configurations. We analyse how the actual possible sensing of the environment influences the dynamics by recovering the appropriate macroscopic limits and by integrating numerically the kinetic transport equation.

Kinetic models with non-local sensing determining cell polarization and speed according to independent cues.

Cells move by run and tumble, a kind of dynamics in which the cell alternates runs over straight lines and re-orientations. This erratic motion may be influenced by external factors, like chemicals, nutrients, the extra-cellular matrix, in the sense that the cell measures the external field and elaborates the signal eventually adapting its dynamics. We propose a kinetic transport equation implementing a velocity-jump process in which the transition probability takes into account a double bias, which acts, respectively, on the choice of the direction of motion and of the speed. The double bias depends on two different non-local sensing cues coming from the external environment. We analyze how the size of the cell and the way of sensing the environment with respect to the variation of the external fields affect the cell population dynamics by recovering an appropriate macroscopic limit and directly integrating the kinetic transport equation. A comparison between the solutions of the transport equation and of the proper macroscopic limit is also performed.