arXiv subjects

Matthew J Simpson

Publications and source records attributed to Matthew J Simpson.

28 records · Page 2Linked to original sources

arXiv2020

Invading and receding sharp-fronted travelling waves

Biological invasion, whereby populations of motile and proliferative individuals lead to moving fronts that invade into vacant regions, are routinely studied using partial differential equation (PDE) models based upon the classical Fisher--KPP model. While the Fisher--KPP model and extensions have been successfully used to model a range of invasive phenomena, including ecological and cellular invasion, an often--overlooked limitation of the Fisher--KPP model is that it cannot be used to model biological recession where the spatial extent of the population decreases with time. In this work we study the \textit{Fisher--Stefan} model, which is a generalisation of the Fisher--KPP model obtained by reformulating the Fisher--KPP model as a moving boundary problem. The nondimensional Fisher--Stefan model involves just one single parameter, $κ$, which relates the shape of the density front at the moving boundary to the speed of the associated travelling wave, $c$. Using numerical simulation, phase plane and perturbation analysis, we construct approximate solutions of the Fisher--Stefan model for both slowly invading and slowly receding travelling waves, as well as for rapidly receding travelling waves. These approximations allow us to determine the relationship between $c$ and $κ$ so that commonly--reported experimental estimates of $c$ can be used to provide estimates of the unknown parameter $κ$. Interestingly, when we reinterpret the Fisher--KPP model as a moving boundary problem, many disregarded features of the classical Fisher--KPP phase plane take on a new interpretation since travelling waves solutions with $c < 2$ are not normally considered. This means that our analysis of the Fisher--Stefan model has both practical value and an inherent mathematical value.

q-bio.TO↗

arXiv2020

Exact sharp-fronted travelling wave solutions of the Fisher-KPP equation

A family of travelling wave solutions to the Fisher-KPP equation with speeds $c=\pm 5/\sqrt{6}$ can be expressed exactly using Weierstrass elliptic functions. The well-known solution for $c=5/\sqrt{6}$, which decays to zero in the far-field, is exceptional in the sense that it can be written simply in terms of an exponential function. This solution has the property that the phase-plane trajectory is a heteroclinic orbit beginning at a saddle point and ends at the origin. For $c=-5/\sqrt{6}$, there is also a trajectory that begins at the saddle point, but this solution is normally disregarded as being unphysical as it blows up for finite $z$. We reinterpret this special trajectory as an exact sharp-fronted travelling solution to a \textit{Fisher-Stefan} type moving boundary problem, where the population is receding from, instead of advancing into, an empty space. By simulating the full moving boundary problem numerically, we demonstrate how time-dependent solutions evolve to this exact travelling solution for large time. The relevance of such receding travelling waves to mathematical models for cell migration and cell proliferation is also discussed.

nlin.PS↗

arXiv2020

Travelling waves in a free boundary mechanobiological model of an epithelial tissue

We consider a free boundary model of epithelial cell migration with logistic growth and nonlinear diffusion induced by mechanical interactions. Using numerical simulations, phase plane and perturbation analysis, we find and analyse travelling wave solutions with negative, zero, and positive wavespeeds. Unlike classical travelling wave solutions of reaction-diffusion equations, the travelling wave solutions that we explore have a well-defined front and are not associated with a heteroclinic orbit in the phase plane. We find leading order expressions for both the wavespeed and the density at the free boundary. Interestingly, whether the travelling wave solution invades or retreats depends only on whether the carrying capacity density corresponds to cells being in compression or extension.

nlin.PS↗

arXiv2020

A sharp-front moving boundary model for malignant invasion

We analyse a novel mathematical model of malignant invasion which takes the form of a two-phase moving boundary problem describing the invasion of a population of malignant cells into a population of background tissue, such as skin. Cells in both populations undergo diffusive migration and logistic proliferation. The interface between the two populations moves according to a two-phase Stefan condition. Unlike many reaction-diffusion models of malignant invasion, the moving boundary model explicitly describes the motion of the sharp front between the cancer and surrounding tissues without needing to introduce degenerate nonlinear diffusion. Numerical simulations suggest the model gives rise to very interesting travelling wave solutions that move with speed $c$, and the model supports both malignant invasion and malignant retreat, where the travelling wave can move in either the positive or negative $x$-directions. Unlike the well-studied Fisher-Kolmogorov and Porous-Fisher models where travelling waves move with a minimum wave speed $c \ge c^* > 0$, the moving boundary model leads to travelling wave solutions with $|c| < c^{**}$. We interpret these travelling wave solutions in the phase plane and show that they are associated with several features of the classical Fisher-Kolmogorov phase plane that are often disregarded as being nonphysical. We show, numerically, that the phase plane analysis compares well with long time solutions from the full partial differential equation model as well as providing accurate perturbation approximations for the shape of the travelling waves.

nlin.PS↗

arXiv2020

Critical length for the spreading-vanishing dichotomy in higher dimensions

We consider an extension of the classical Fisher-Kolmogorov equation, called the \textit{Fisher-Stefan} model, which is a moving boundary problem on $0 < x < L(t)$. A key property of the Fisher-Stefan model is the \textit{spreading-vanishing dichotomy}, where solutions with $L(t) > L_{\textrm{c}}$ will eventually spread as $t \to \infty$, whereas solutions where $L(t) \ngtr L_{\textrm{c}}$ will vanish as $t \to \infty$. In one dimension is it well-known that the critical length is $L_{\textrm{c}} = π/2$. In this work we re-formulate the Fisher-Stefan model in higher dimensions and calculate $L_{\textrm{c}}$ as a function of spatial dimensions in a radially symmetric coordinate system. Our results show how $L_{\textrm{c}}$ depends upon the dimension of the problem and numerical solutions of the governing partial differential equation are consistent with our calculations.

nlin.PS↗

arXiv2019

Hole-closing model reveals exponents for nonlinear degenerate diffusivity functions in cell biology

Continuum mathematical models for collective cell motion normally involve reaction-diffusion equations, such as the Fisher-KPP equation, with a linear diffusion term to describe cell motility and a logistic term to describe cell proliferation. While the Fisher-KPP equation and its generalisations are commonplace, a significant drawback for this family of models is that they are not able to capture the moving fronts that arise in cell invasion applications such as wound healing and tumour growth. An alternative, less common, approach is to include nonlinear degenerate diffusion in the models, such as in the Porous-Fisher equation, since solutions to the corresponding equations have compact support and therefore explicitly allow for moving fronts. We consider here a hole-closing problem for the Porous-Fisher equation whereby there is initially a simply connected region (the hole) with a nonzero population outside of the hole and a zero population inside. We outline how self-similar solutions (of the second kind) describe both circular and non-circular fronts in the hole-closing limit. Further, we present new experimental and theoretical evidence to support the use of nonlinear degenerate diffusion in models for collective cell motion. Our methodology involves setting up a 2D wound healing assay that has the geometry of a hole-closing problem, with cells initially seeded outside of a hole that closes as cells migrate and proliferate. For a particular class of fibroblast cells, the aspect ratio of an initially rectangular wound increases in time, so the wound becomes longer and thinner as it closes; our theoretical analysis shows that this behaviour is consistent with nonlinear degenerate diffusion but is not able to be captured with commonly used linear diffusion. This work is important because it provides a clear test for degenerate diffusion over linear diffusion in cell lines.

physics.bio-ph↗

arXiv2019

Reversible signal transmission in an active mechanical metamaterial

Mechanical metamaterials are designed to enable unique functionalities, but are typically limited by an initial energy state and require an independent energy input to function repeatedly. Our study introduces a theoretical active mechanical metamaterial that incorporates a biological reaction mechanism to overcome this key limitation of passive metamaterials. Our material allows for reversible mechanical signal transmission, where energy is reintroduced by the biologically motivated reaction mechanism. By analysing a coarse grained continuous analogue of the discrete model, we find that signals can be propagated through the material by a travelling wave. Analysis of the continuum model provides the region of the parameter space that allows signal transmission, and reveals similarities with the well-known FitzHugh-Nagumo system. We also find explicit formulae that approximate the effect of the timescale of the reaction mechanism on the signal transmission speed, which is essential for controlling the material.

cond-mat.soft↗

arXiv2018

Rapid calculation of maximum particle lifetime for diffusion in complex geometries

Diffusion of molecules within biological cells and tissues is strongly influenced by crowding. A key quantity to characterize diffusion is the particle lifetime, which is the time taken for a diffusing particle to exit by hitting an absorbing boundary. Calculating the particle lifetime provides valuable information, for example, by allowing us to compare the timescale of diffusion and the timescale of reaction, thereby helping us to develop appropriate mathematical models. Previous methods to quantify particle lifetimes focus on the mean particle lifetime. Here, we take a different approach and present a simple method for calculating the maximum particle lifetime. This is the time after which only a small specified proportion of particles in an ensemble remain in the system. Our approach produces accurate estimates of the maximum particle lifetime, whereas the mean particle lifetime always underestimates this value compared with data from stochastic simulations. Furthermore, we find that differences between the mean and maximum particle lifetimes become increasingly important when considering diffusion hindered by obstacles.

physics.bio-ph↗

arXiv2017

The role of initial geometry in experimental models of wound closing

Wound healing assays are commonly used to study how populations of cells, initialised on a two-dimensional surface, act to close an artificial wound space. While real wounds have different shapes, standard wound healing assays often deal with just one simple wound shape, and it is unclear whether varying the wound shape might impact how we interpret results from these experiments. In this work, we describe a new kind of wound healing assay, called a sticker assay, that allows us to examine the role of wound shape in a series of wound healing assays performed with fibroblast cells. In particular, we show how to use the sticker assay to examine wound healing with square, circular and triangular shaped wounds. We take a standard approach and report measurements of the size of the wound as a function of time. This shows that the rate of wound closure depends on the initial wound shape. This result is interesting because the only aspect of the assay that we change is the initial wound shape, and the reason for the different rate of wound closure is unclear. To provide more insight into the experimental observations we describe our results quantitatively by calibrating a mathematical model, describing the relevant transport phenomena, to match our experimental data. Overall, our results suggest that the rates of cell motility and cell proliferation from different initial wound shapes are approximately the same, implying that the differences we observe in the wound closure rate are consistent with a fairly typical mathematical model of wound healing. Our results imply that parameter estimates obtained from an experiment performed with one particular wound shape could be used to describe an experiment performed with a different shape. This fundamental result is important because this assumption is often invoked, but never tested.

q-bio.CB↗

arXiv2017

Calculating groundwater response times for flow in heterogeneous porous media

Predicting the amount of time required for a transient groundwater response to take place is a practical question that is of interest in many situations. This time scale is often called the response time. In the groundwater hydrology literature there are two main methods used to calculate the response time: (i) both the transient and steady state groundwater flow equations are solved, and the response time is taken to be amount of time required for the transient solution to approach the steady solution within some tolerance; and (ii) simple scaling arguments are adopted. Certain limitations restrict both of these approaches. Here we outline a third method, based on the theory of mean action time. We derive the governing boundary value problem for both the mean and variance of action time for confined flow in two-dimensional heterogeneous porous media. Importantly, we show that these boundary value problems can be solved using widely available software. Applying these methods to a test case reveals the advantages of the theory of mean action time relative to standard methods.

physics.flu-dyn↗