Computational modelling of epithelial cell monolayers during infection with Listeria monocytogenes

Abstract

Intracellular bacterial infections alter the normal functionality of human host cells and tissues. Infection can also modify the mechanical properties of host cells, altering the mechanical equilibrium of tissues. In order to advance our understanding of host–pathogen interactions, simplified in vitro models are normally used. However, in vitro studies present certain limitations that can be alleviated by the use of computer-based models. As complementary tools these computational models, in conjunction with in vitro experiments, can enhance our understanding of the mechanisms of action underlying infection processes. In this work, we extend our previous computer-based model to simulate infection of epithelial cells with the intracellular bacterial pathogen Listeria monocytogenes. We found that forces generated by host cells play a regulatory role in the mechanobiological response to infection. After infection, in silico cells alter their mechanical properties in order to achieve a new mechanical equilibrium. The model pointed the key role of cell–cell and cell–extracellular matrix interactions in the mechanical competition of bacterial infection. The obtained results provide a more detailed description of cell and tissue responses to infection, and could help inform future studies focused on controlling bacterial dissemination and the outcome of infection processes.