Modelagem computacional da migração de células aderentes em meios porosos

Abstract

Cell migration is an important process in biological phenomena such as wound healing and tumor metastasis, which can be stimulated by mechanical factors. The sensibility of the cell to these stimuli is denoted called mechanosensing, and governs the cellular response to the extracellular mechanical environment. Interstitial fluid, which fills the extracellular matrix, may also influence the mechanical response of the cell due to shear forces. One tool capable of representing the influence of the interstitial fluid on cell migration is computational modeling. In this work, it is presenting a mechanobiological model of adherent cell migration based on mechanosensing, including the influence of the interstitial fluid on the cellular response. A system of differential equations was formulated, implemented and solved that represent the cellular migration process using the finite element method for three different cases. The cellular behavior in an elastic matrix (case 1) and the poroelastic matrix (case 2) was studied. The third case was the study of tumor cells in a microfluidic device with the presence of an interstitial fluid flow and was based on a previous experimental study, which reported the movement of the cells against the flow. The results for elastic and poroelastic models (cases 1 e 2) showed to a migration towards the more strained regions of the ECM, while those of the microfluidic study reported a behavior of cell migration against the flow. The developed mechanosensing model was able to predict the biological behavior of adherent cells in the presence of interstitial fluid, proving to be a useful tool for the study of cell migration.