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Nikolaos Sfakianakis

Publications and source records attributed to Nikolaos Sfakianakis.

18 recordsLinked to original sources

Beyond Classical Diffusion: Fractional Derivatives in Transport and Stochastic Systems

Integer-order differential operators were originally used to describe local and isotropic effects, in both space and time. However, in fields like biology, the modelling of complex phenomena with spatial heterogeneity necessitates more advanced approaches. The fractional calculus framework provides powerful tools for developing models that better capture the intricate dynamics of biological systems. This paper derives fractional reaction-diffusion equations from continuous-time random walks, highlighting the role of heavy-tailed distributions in the process. Both fractional partial differential equations, on the macroscopic level, as well as fractional stochastic differential equations, on the microscopic level, will be derived and simulated from, for simple Riesz-fractional diffusion models. A new numerical scheme that implements periodic boundary conditions is proposed to control the loss of mass density. We highlight the key differences between fractional and classical diffusion.

math.DS↗

Mathematical modelling of cancer invasion: Phenotypic transitioning provides insight into multifocal foci formation

The transition from the epithelial to mesenchymal phenotype and its reverse (from mesenchymal to epithelial) are crucial processes necessary for the progression and spread of cancer. In this paper, we investigate how phenotypic switching at the cancer cell level impacts on behaviour at the tissue level, specifically on the emergence of isolated foci of the invading solid tumour mass leading to a multifocal tumour. To this end, we propose a new mathematical model of cancer invasion that includes the influence of cancer cell phenotype on the rate of invasion and metastasis. The implications of model are explored through numerical simulations revealing that the plasticity of tumour cell phenotypes appears to be crucial for disease progression and local invasive spread. The computational simulations show the progression of the invasive spread of a primary cancer reminiscent of in vivo multifocal breast carcinomas, where multiple, synchronous, ipsilateral neoplastic foci are frequently observed and are associated with a poorer patient prognosis.

q-bio.TO↗

An adaptive rectangular mesh administration and refinement technique with application in cancer invasion models

We present an administration technique for the bookkeeping of adaptive mesh refinement on (hyper-)rectangular meshes. Our technique is a unified approach for h-refinement on 1-, 2- and 3D domains, which is easy to use and avoids traversing the connectivity graph of the ancestry of mesh cells. Due to the employed rectangular mesh structure, the identification of the siblings and the neighbouring cells is greatly simplified. The administration technique is particularly designed for smooth meshes, where the smoothness is dynamically used in the matrix operations. It has a small memory footprint that makes it affordable for a wide range of mesh resolutions over a large class of problems. We present three applications of this technique, one of which addresses h-refinement and its benefits in a 2D tumour growth and invasion problem.

math.NA↗

Multiscale modeling of glioma invasion: from receptor binding to flux-limited macroscopic PDEs

We propose a novel approach to modeling cell migration in an anisotropic environment with biochemical heterogeneity and interspecies interactions, using as a paradigm glioma invasion in brain tissue under the influence of hypoxia-triggered angiogenesis. The multiscale procedure links single-cell and mesoscopic dynamics with population level behavior, leading on the macroscopic scale to flux-limited glioma diffusion and multiple taxis. We verify the non-negativity of regular solutions (provided they exist) to the obtained macroscopic PDE-ODE system and perform numerical simulations to illustrate the solution behavior under several scenarios.

q-bio.TO↗

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↗

Modelling cell-cell collision and adhesion with the Filament Based Lamellipodium Model

We extend the live-cell motility Filament Based Lamellipodium Model to incorporate the forces exerted on the lamellipodium of the cells due to cell-cell collision and cadherin induced cell-cell adhesion. We take into account the nature of these forces via physical and biological constraints and modelling assumptions. We investigate the effect these new components have in the migration and morphology of the cells through particular experiments. We exhibit moreover the similarities between our simulated cells and HeLa cancer cells.

q-bio.CB↗

A Hybrid Multiscale Model for Cancer Invasion of the Extracellular Matrix

The ability to locally degrade the extracellular matrix (ECM) and interact with the tumour microenvironment is a key process distinguishing cancer from normal cells, and is a critical step in the metastatic spread of the tumour. The invasion of the surrounding tissue involves the coordinated action between cancer cells, the ECM, the matrix degrading enzymes, and the epithelial-to-mesenchymal transition (EMT). This is a regulatory process through which epithelial cells (ECs) acquire mesenchymal characteristics and transform to mesenchymal-like cells (MCs). In this paper, we present a new mathematical model which describes the transition from a collective invasion strategy for the ECs to an individual invasion strategy for the MCs. We achieve this by formulating a coupled hybrid system consisting of partial and stochastic differential equations that describe the evolution of the ECs and the MCs, respectively. This approach allows one to reproduce in a very natural way fundamental qualitative features of the current biomedical understanding of cancer invasion that are not easily captured by classical modelling approaches, for example, the invasion of the ECM by self-generated gradients and the appearance of EC invasion islands outside of the main body of the tumour.

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Stability, convergence, and sensitivity analysis of the Filament Based Lamellipodium Model and the corresponding FEM

This paper focuses on the study of the Filament Based Lamellipodium Model (FBLM) and the corresponding Finite Element Method (FEM) from a numerical point of view. We study fundamental numerical properties of the FEM and justify the further use of the FBLM. We exhibit that the FEM satisfies a timestep stability condition that is consistent with the nature of the problem. We propose a particular strategy to automatically adapt the time step of the method. We show that the FEM convergences with respect to the (two-dimensional) space discretization in a series of characteristic and representative experiments. We embed and couple the FBLM with a complex extracellular environment comprised of chemical and haptic components and study their combined time evolution. Under this prism, we study the sensitivity of the FBLM on several of its controlling parameters and discuss their influence in the development of the model.

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Existence and uniqueness of global classical solutions to a two species cancer invasion haptotaxis model

We consider a haptotaxis cancer invasion model that includes two families of cancer cells. Both families, migrate on the extracellular matrix and proliferate. Moreover the model describes an epithelial-to-mesenchymal-like transition between the two families, as well as a degradation and a self-reconstruction process of the extracellular matrix. We prove positivity and conditional global existence and uniqueness of the classical solutions of the problem for large initial data.

math.AP↗

Chemotaxis and Haptotaxis on Cellular Level

Chemotaxis and haptotaxis have been a main theme in the macroscopic study of bacterial and cellular motility. In this work we investigate the influence these processes have on the shape and motility of fast migrating cells. We note that despite their biological and modelling differences, the cells exhibit many similarities in their migration. We moreover see, that after an initial adjustment phase, the cells obtain a stable shape and their motion is similar to advection.

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Energy intake functions of ectotherms and endotherms derived from their body mass growth

How animals allocate energy to different body functions is still not completely understood and a challenging topic until recently. Here, we investigate in more detail the allocation of energy intake to growth, reproduction or heat production by developing energy budget models for ectothermic and endothermic vertebrates using a mathematical approach. We calculated energy intake functions of ectotherms and endotherms derived from their body mass growth. We show that our energy budget model produces energy intake patterns and distributions as observed in ectothermic and endothermic species. Our results comply consistently with some empirical studies that in endothermic species, like birds and mammals, energy is used for heat production instead of growth. Our model additionally offers an explanation on known differences in absolute energy intake between ectothermic fish and reptiles and endothermic birds and mammals. From a mathematical point of view, the model comes in two equivalent formulations, a differential and an integral one. It is derived from a discrete level approach, and it is shown to be well-posed and to attain a unique solution for (almost) every parameter set. Numerically, the integral formulation of the model is considered as an inverse problem with unknown parameters that are estimated using a series of experiments/realistic data.

q-bio.PE↗

Numerical simulation of a contractivity based multiscale cancer invasion model

We present a problem-suited numerical method for a particularly challenging cancer invasion model. This model is a multiscale haptotaxis advection-reaction-diffusion system that describes the macroscopic dynamics of two types of cancer cells coupled with microscopic dynamics of the cells adhesion on the extracellular matrix. The difficulties to overcome arises from the non-constant advection and diffusion coefficients, a time delay term, as well as stiff reaction terms. Our numerical method is a second order finite volume implicit-explicit scheme adjusted to include a) non-constant diffusion coefficients in the implicit part, b) an interpolation technique for the time delay, and c) a restriction on the time increment for the stiff reaction terms.

math.NA↗

A multiscale approach to the migration of cancer stem cells: mathematical modelling and simulations

We propose a multiscale model of the invasion of the extracellular matrix by two types of cancer cells, the differentiated cancer cells and the cancer stem cells. We assume that the epithelial mesenchymal-like transition between them is driven primarily by the epidermal growth factors. We moreover take into account the transidifferentiation program of the cancer stem cells and the cancer associated fibroblast cells as well as the fibroblast-driven remodelling of the extracellular matrix. The proposed haptotaxis model combines the macroscopic phenomenon of the invasion of the extracellular matrix with the microscopic dynamics of the epidermal growth factors. We analyse our model in a component-wise manner and compare our findings with the literature. We investigate pathological situations regarding the epidermal growth factors and accordingly propose "mathematical-treatment" scenarios to control the aggressiveness of the tumour.

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A mathematical insight in the epithelial-mesenchymal-like transition in cancer cells and its effect in the invasion of the extracellular matrix

Current biological knowledge supports the existence of a secondary group of cancer cells within the body of the tumour that exhibits stem cell-like properties. These cells are termed Cancer Stem Cells (CSCs}, and as opposed to the more usual Differentiated Cancer Cells (DCCs), they exhibit higher motility, they are more resilient to therapy, and are able to metastasize to secondary locations within the organism and produce new tumours. The origin of the CSCs is not completely clear; they seem to stem from the DCCs via a transition process related to the Epithelial-Mesenchymal Transition (EMT) that can also be found in normal tissue. In the current work we model and numerically study the transition between these two types of cancer cells, and the resulting "ensemble" invasion of the extracellular matrix. This leads to the derivation and numerical simulation of two systems: an algebraic-elliptic system for the transition and an advection-reaction-diffusion system of Keller-Segel taxis type for the invasion.

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An Extended Filament Based Lamellipodium Model Produces Various Moving Cell Shapes in the Presence of Chemotactic Signals

The Filament Based Lamellipodium Model (FBLM) is a two-phase two-dimensional continuum model, describing the dynamcis of two interacting families of locally parallel actin filaments (C.Schmeiser and D.Oelz, How do cells move? Mathematical modeling of cytoskeleton dynamics and cell migration. Cell mechanics: from single scale-based models to multiscale modeling. Chapman and Hall, 2010). It contains accounts of the filaments' bending stiffness, of adhesion to the substrate, and of cross-links connecting the two families. An extension of the model is presented with contributions from nucleation of filaments by branching, from capping, from contraction by actin-myosin interaction, and from a pressure-like repulsion between parallel filaments due to Coulomb interaction. The effect of a chemoattractant is described by a simple signal transduction model influencing the polymerization speed. Simulations with the extended model show its potential for describing various moving cell shapes, depending on the signal transduction procedure, and for predicting transients between nonmoving and moving states as well as changes of direction.

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Numerical study of cancer cell invasion dynamics using adaptive mesh refinement: the urokinase model

In the present work we investigate the chemotactically and proteolytically driven tissue invasion by cancer cells. The model employed is a system of advection-reaction-diffusion equations that features the role of the serine protease urokinase-type plasminogen activator. The analytical and numerical study of this system constitutes a challenge due to the merging, emerging, and travelling concentrations that the solutions exhibit. Classical numerical methods applied to this system necessitate very fine discretization grids to resolve these dynamics in an accurate way. To reduce the computational cost without sacrificing the accuracy of the solution, we apply adaptive mesh refinement techniques, in particular h-refinement. Extended numerical experiments exhibit that this approach provides with a higher order, stable, and robust numerical method for this system. We elaborate on several mesh refinement criteria and compare the results with the ones in the literature. We prove, for a simpler version of this model, $L^\infty$ bounds for the solutions, we study the stability of its conditional steady states, and conclude that it can serve as a test case for further development of mesh refinement techniques for cancer invasion simulations.

math.NA↗

Entropy dissipation of moving mesh adaptation

Non-uniform grids and mesh adaptation have been a growing part of numerical simulation over the past years. It has been experimentally noted that mesh adaptation leads not only to locally improved solution but also to numerical stability of the underlying method. There have been though only few results on the mathematical analysis of these schemes due to the lack of proper tools that incorporate both the time evolution and the mesh adaptation step of the overall algorithm. In this paper we provide a method to perform the analysis of the mesh adaptation method, including both the mesh reconstruction and evolution of the solution. We moreover employ this method to extract sufficient conditions -on the adaptation of the mesh- that stabilize a numerical scheme in the sense of the entropy dissipation.

math.NA↗

Adaptive mesh reconstruction: Total Variation Bound

We consider 3-point numerical schemes for scalar Conservation Laws, that are oscillatory either to their dispersive or anti-diffusive nature. Oscillations are responsible for the increase of the Total Variation (TV); a bound on which is crucial for the stability of the numerical scheme. It has been noticed (\cite{Arvanitis.2001}, \cite{Arvanitis.2004}, \cite{Sfakianakis.2008}) that the use of non-uniform adaptively redefined meshes, that take into account the geometry of the numerical solution itself, is capable of taming oscillations; hence improving the stability properties of the numerical schemes. In this work we provide a model for studying the evolution of the extremes over non-uniform adaptively redefined meshes. Based on this model we prove that proper mesh reconstruction is able to control the oscillations; we provide bounds for the Total Variation (TV) of the numerical solution. We moreover prove under more strict assumptions that the increase of the TV -due to the oscillatory behaviour of the numerical schemes- decreases with time; hence proving that the overall scheme is TV Increase-Decreasing (TVI-D).

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