arXiv subjects

Christina Surulescu

Publications and source records attributed to Christina Surulescu.

29 records · Page 2Linked to original sources

arXiv2020

Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment

Gliomas are primary brain tumors with a high invasive potential and infiltrative spread. Among them, glioblastoma multiforme (GBM) exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Histological samples showing garland-like hypercellular structures (so-called pseudopalisades) centered around the occlusion site of a capillary are typical for GBM and hint on poor prognosis of patient survival. We propose a multiscale modeling approach in the kinetic theory of active particles framework and deduce by an upscaling process a reaction-diffusion model with repellent pH-taxis. We prove existence of a unique global bounded classical solution for a version of the obtained macroscopic system and investigate the asymptotic behavior of the solution. Moreover, we study two different types of scaling and compare the behavior of the obtained macroscopic PDEs by way of simulations. These show that patterns1 (including pseudopalisades) can be formed for some parameter ranges, in accordance with the tumor grade. This is true when the PDEs are obtained via parabolic scaling (undirected tissue), while no such patterns are observed for the PDEs arising by a hyperbolic limit (directed tissue). This suggests that brain tissue might be undirected - at least as far as glioma migration is concerned. We also investigate two different ways of including cell level descriptions of response to hypoxia and the way they are related.

q-bio.TO↗

arXiv2020

Modeling multiple taxis: tumor invasion with phenotypic heterogeneity, haptotaxis, and unilateral interspecies repellence

We provide a short review of existing models with multiple taxis performed by (at least) one species and consider a new mathematical model for tumor invasion featuring two mutually exclusive cell phenotypes (migrating and proliferating). The migrating cells perform nonlinear diffusion and two types of taxis in response to non-diffusing cues: away from proliferating cells and up the gradient of surrounding tissue. Transitions between the two cell subpopulations are influenced by subcellular (receptor binding) dynamics, thus conferring the setting a multiscale character. We prove global existence of weak solutions to a simplified model version and perform numerical simulations for the full setting under several phenotype switching and motility scenarios. We also compare (via simulations) this model with the corresponding haptotaxis-chemotaxis one featuring indirect chemorepellent production and provide a discussion about possible model extensions and mathematical challenges.

math.AP↗

arXiv2020

Global existence, asymptotic behavior, and pattern formation driven by the parametrization of a nonlocal Fisher-KPP problem

The global boundedness and the hair trigger effect of solutions for the nonlinear nonlocal reaction-diffusion equation \begin{align*} u_t=Δu+μu^α(1-κJ*u^β),\quad\hbox{in} \;\mathbb R^N\times(0,\infty),\; N\geq 1 \end{align*} with $α\geq1$, $β,μ,κ>0$ and $u(x,0)=u_0(x)$ are investigated. Under appropriate assumptions on $J$, it is proved that for any nonnegative and bounded initial condition, if $α\in[1,α^*)$ with $α^*=1+β$ for $N=1,2$ and $α^*=1+\frac{2β}{N}$ for $N>2$, then the problem has a global bounded classical solution. Under further assumptions on the initial datum, the solutions satisfying $0\leq u(x,t)\leqκ^{-\frac1β}$ for any $(x,t)\in\mathbb R^N\times[0,+\infty)$ are shown to converge to $κ^{-\frac1β}$ uniformly on any compact subset of $\mathbb R^N$, which is known as the hair trigger effect. 1D numerical simulations of the above nonlocal reaction-diffusion equation are performed and the effect of several combinations of parameters and convolution kernels on the solution behavior is investigated. The results motivate a discussion about some conjectures arising from this model and further issues to be studied in this context. A formal deduction of the model from a mesoscopic formulation is provided as well.

math.AP↗

arXiv2019

Nonlocal and local models for taxis in cell migration: a rigorous limit procedure

A rigorous limit procedure is presented which links nonlocal models involving adhesion or nonlocal chemotaxis to their local counterparts featuring haptotaxis and classical chemotaxis, respectively. It relies on a novel reformulation of the involved nonlocalities in terms of integral operators applied directly to the gradients of signal-dependent quantities. The proposed approach handles both model types in a unified way and extends the previous mathematical framework to settings that allow for general solution-dependent coefficient functions. The previous forms of nonlocal operators are compared with the new ones introduced in this paper and the advantages of the latter are highlighted by concrete examples. Numerical simulations in 1D provide an illustration of some of the theoretical findings.

math.AP↗

arXiv2019

Mathematical models for cell migration: a nonlocal perspective

We provide a review of recent advancements in nonlocal continuous models for migration, mainly from the perspective of its involvement in embryonal development and cancer invasion. Particular emphasis is placed on spatial nonlocality occurring in advection terms, used to characterise a cell's motility bias according to its interactions with other cellular and acellular components in its vicinity (e.g., cell-cell and cell-tissue adhesions, nonlocal chemotaxis), but we also shortly address spatially nonlocal source terms. Following a brief introduction and motivation, we give a systematic classification of available PDE models with respect to the type of featured nonlocalities and review some of the mathematical challenges arising from such models, with a focus on analytical aspects. Keywords: cell-cell and cell-tissue adhesion; nonlocal and local chemotaxis; haptotaxis; classes of nonlocal models; integro-differential equations; mathematical challenges.

math.AP↗

arXiv2019

Does indirectness of signal production reduce the explosion-supporting potential in chemotaxis-haptotaxis systems? Global classical solvability in a class of models for cancer invasion (and more)

We propose and study a class of parabolic-ODE models involving chemotaxis and haptotaxis of a species following signals indirectly produced by another, non-motile one. The setting is motivated by cancer invasion mediated by interactions with the tumor microenvironment, but has much wider applicability, being able to comprise descriptions of biologically quite different problems. As a main mathematical feature consituting a core difference to both classical Keller-Segel chemotaxis systems and Chaplain-Lolas type chemotaxis-haptotaxis systems, the considered model accounts for certain types of indirect signal production mechanisms. The main results assert unique global classical solvability under suitably mild assumptions on the system parameter functions in associated spatially two-dimensional initial-boundary value problems. In particular, this rigorously confirms that at least in two-dimensional settings, the considered indirectness in signal production induces a significant blow-up suppressing tendency also in taxis systems substantially more general than some particular examples for which corresponding effects have recently been observed.

math.AP↗

arXiv2019

On a model for epidemic spread with interpopulation contact and repellent taxis

We study a PDE model for dynamics of susceptible-infected interactions. The dispersal of susceptibles is via diffusion and repellent taxis as they move away from the increasing density of infected. The diffusion of infected is a nonlinear, possibly degenerating term in nondivergence form. We prove the existence of so-called weak-strong solutions in 1D for a positive susceptible initial population. For dimension $N\geq 2$ and nonnegative susceptible initial density we show the existence of supersolutions. Numerical simulations are performed for different scenarios and illustrate the space-time behaviour of solutions.

math.AP↗

arXiv2018

Higher-order models for glioma invasion: from a two-scale description to effective equations for mass density and momentum

Starting from a two-scale description involving receptor binding dynamics and a kinetic transport equation for the evolution of the cell density function under velocity reorientations, we deduce macroscopic models for glioma invasion featuring partial differential equations for the mass density and momentum of a population of glioma cells migrating through the anisotropic brain tissue. The proposed first and higher order moment closure methods enable numerical simulations of the kinetic equation. Their performance is then compared to that of the diffusion limit. The approach allows for DTI-based, patient-specific predictions of the tumor extent and its dynamic behavior.

math.NA↗

arXiv2016

Global existence for a degenerate haptotaxis model of tumor invasion under the go-or-grow dichotomy hypothesis

We propose and study a strongly coupled PDE-ODE-ODE system modeling cancer cell invasion through a tissue network under the go-or-grow hypothesis asserting that cancer cells can either move or proliferate. Hence our setting features two interacting cell populations with their mutual transitions and involves tissue-dependent degenerate diffusion and haptotaxis for the moving subpopulation. The proliferating cells and the tissue evolution are characterized by way of ODEs for the respective densities. We prove the global existence of weak solutions and illustrate the model behaviour by numerical simulations in a two-dimensional setting.

math.AP↗

arXiv2016

Global weak solutions to a strongly degenerate haptotaxis model

We consider a one-dimensional version of a model obtained in [C. Engwer, A. Hunt, and C. Surulescu: Effective equations for anisotropic glioma spread with proliferation: a multiscale approach and comparisons with previous settings, IMA J. Math. Med. Biol. (2015), doi: 10.1093/imammb/dqv030] and describing the anisotropic spread of tumor cells in a tissue network. The model consists of a reaction-diffusion-taxis equation for the density of tumor cells coupled with an ODE for the density of tissue fibers and allows for strong degeneracy both in the diffusion and the haptotaxis terms. In this setting we prove the global existence of weak solutions to an associated no-flux initial-boundary value problem.

math.AP↗

arXiv2015

Global existence for a degenerate haptotaxis model of cancer invasion

We propose and study a strongly coupled PDE-ODE system with tissue-dependent degenerate diffusion and haptotaxis that can serve as a model prototype for cancer cell invasion through the extracellular matrix. We prove the global existence of weak solutions and illustrate the model behaviour by numerical simulations for a two-dimensional setting.

math.AP↗