Effects along the epithelial-mesenchymal biointerface in direct cell self-organisation : multiscale theoretical analysis

Pajic-Lijakovic, Ivana and Milivojevic, Milan and McClintock, Peter V.E. (2026) Effects along the epithelial-mesenchymal biointerface in direct cell self-organisation : multiscale theoretical analysis. BioSystems. ISSN 0303-2647 (In Press)

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Abstract

Epithelial cancer ranks among the most deadly types of cancer globally. Focusing on the disease's early stages could lead to significant enhancements in the survival rates of cancer patients. The initial phase of the disease is associated with the dissemination of cancer cells into the adjacent healthy epithelium. Therefore, a more profound understanding of cell dynamics at the biointerface between epithelial and cancer (mesenchymal) cells is essential for managing the disease promptly. The dynamics of cells at this epithelial-cancer biointerface arises through interplay between a variety of biological and physical mechanisms. Although considerable research has been dedicated to examining the spread of cancer cells across the epithelium, the physical mechanisms that govern the dynamics at the biointerface remain poorly understood. The main goal of this multi-scale theoretical consideration is to emphasize the influence of physical factors, such as the viscoelasticity of the subpopulations and the dilational viscoelasticity of the biointerface, on the efficiency with which cancer spreads through the epithelium. We do so by consideration of the mechanical coupling between the epithelial and cancer mesenchymal-like subpopulations. In this review, we consider this complex phenomenon from a multiscale mechanical perspective that has not been explicitly addressed in earlier studies, using model systems such as the segregation of co-cultured epithelial–mesenchymal spheroids. The mechanical-coupling between the subpopulations arising from the system’s viscoelasticity is discussed from the cellular to supracellular levels in order to recognize the main physical factors responsible for the spreading of cancer.