Nonlocal multiscale modelling of tumour-oncolytic viruses interactions within a heterogeneous fibrous/non-fibrous extracellular matrix

Abstract

In this study we investigate computationally tumour-oncolytic virus (OV) interactions that take place within a heterogeneous extracellular matrix (ECM). The ECM is viewed as a mixture of two constitutive phases, namely a fibre phase and a non-fibre phase. The multiscale mathematical model presented here focuses on the nonlocal cell-cell and cell-ECM interactions, and how these interactions might be impacted by the infection of cancer cells with the OV. At macroscale we track the kinetics of cancer cells, virus particles and the ECM. At microscale we track (i) the degradation of ECM by matrix degrading enzymes (MDEs) produced by cancer cells, which further influences the movement of tumour boundary; (ii) the re-arrangement of the microfibres that influences the re-arrangement of macrofibres (i.e., fibres at macroscale). With the help of this new multiscale model, we investigate two questions: (i) whether the infected cancer cell fluxes are the result of local or non-local advection in response to ECM density; and (ii) what is the effect of ECM fibres on the the spatial spread of oncolytic viruses and the outcome of oncolytic virotherapy.

Keywords

• multiscale cancer modelling
• non-local cell adhesion
• tumour-oncolytic viruses interactions
• cancer invasion
• computational modelling
• cross cell-cell adhesion
• extracellular matrix fibres