The dynamics along the biointerface between the epithelial and cancer mesenchymal cells: Modeling consideration

Abstract

Epithelial cancer is the one of most lethal cancer type worldwide. Targeting the early stage of disease would allow dramatic improvements in the survival of cancer patients. The early stage of the disease is related to cancer cell spreading across surrounding healthy epithelium. Consequently, deeper insight into cell dynamics along the biointerface between epithelial and cancer (mesenchymal) cells is necessary in order to control the disease as soon as possible. Cell dynamics along this epithelial-cancer biointerface is the result of the interplay between various biological and physical mechanisms. Despite extensive research devoted to study cancer cell spreading across the epithelium, we still do not understand the physical mechanisms which influences the dynamics along the biointerface. These physical mechanisms are related to the interplay between physical parameters such as: (1) interfacial tension between cancer and epithelial subpopulations, (2) established interfacial tension gradients, (3) the bending rigidity of the biointerface and its impact on the interfacial tension, (4) surface tension of the subpopulations, (5) viscoelasticity caused by collective cell migration, and (6) cell residual stress accumulation. The main goal of this study is to review some of these physical parameters in the context of the epithelial/cancer biointerface elaborated on the model system such as the biointerface between breast epithelial MCF-10A cells and cancer MDA-MB-231 cells and then to incorporate these parameters into a new biophysical model that could describe the dynamics of the biointerface. We conclude by discussing three biophysical scenarios for cell dynamics along the biointerface, which can occur depending on the magnitude of the generated shear stress: a smooth biointerface, a slightly-perturbed biointerface and an intensively-perturbed biointerface in the context of the Kelvin-Helmholtz instability. These scenarios are related to the probability of cancer invasion.

Keywords: Cell residual stress accumulation; Collective cell migration; Interfacial tension between epithelial and cancer cells; Tissue surface tension; Viscoelasticity.