Computational model of the cancer necrotic core formation in a tumor-on-a-chip device.

The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.

A mechanobiological model to study upstream cell migration guided by tensotaxis.

Cell migration is a process of crucial importance for the human body. It is responsible for important processes such as wound healing and tumor metastasis. Migration may occur in response to stimuli of chemical, physical and mechanical nature occurring in the cellular microenvironment. The interstitial flow (IF) can generate mechanical stimuli in cells that influence the cell behavior and interactions of the cells with the extracellular matrix (ECM). One of the phenomena is upstream migration, which is observed in some tumors. In this work, we present a new approach to study the adherent cell migration in a porous medium using a mechanobiological model, attempting to understand if upstream migration can be generated exclusively by mechanical factors. The influence of IF on the behavior of cells and the extracellular matrix was considered. The model is based on a system of coupled nonlinear differential equations solved by the finite element method. Several simulations were performed to study the upstream cell migration and evaluate the effects of pressure, permeability, ECM stiffness and cellular concentration variations on the cell velocity. The results indicated that upstream migration can occur in the presence of mechanical stimuli generated by IF and that the tested parameters have a direct influence on the cellular velocity, especially the pressure and the permeability.