Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Wednesday Speaker Abstracts

A HYBRID MODEL OF CELL MONOLAYERS: MAPPING THE MECHANOBIOLOGY OF INFECTION Raul Aparicio-Yuste 1,4 ; Lara Hundsdorfer 1 ; Effie E. Bastounis 1,3 ; Maria Jose Gómez Benito 2 ; 1 Interfaculty Institute of Microbiology and Infection Medicine, Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI, EXC 2124), Universität Tübingen, Tübingen, Germany 2 Aragon Institute of Engineering Research (I3A), University of Zaragoza, Multiscale in Mechanical and Biological Engineering (M2BE), Zaragoza, Spain 3 Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany 4 Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany Bacterial infections are the second leading cause of death worldwide, highlighting the importance of better understanding host defence mechanisms at the tissue level. We investigate how intracellular bacterial infection of epithelial monolayers (EPMs) by food-borne Listeria monocytogenes (L.m.) evolves and what are the physical determinants regulating infection spread. During L.m. infection, uninfected cells collectively take action to eliminate L.m.-infected neighbouring cells through a mechanical competition, that drives the extrusion and onslaught of infected cells. While this process is known to involve coordinated cell motion and changes in cell mechanics, the underlying mechanotransduction mechanisms remain not well understood. To address this issue, we developed a hybrid in silico approach by integrating an agent-based model (ABM) and a finite element model (FEM) to simulate a deformable EPM. In the ABM, cells are represented as mechanosensitive agents that can generate active forces and adapt to local stress. Cell shapes are defined via Voronoi tessellation and then discretized into a FEM to capture tissue-level deformation and stress redistribution. This hybrid, iterative approach enables collective behaviours to emerge from single-cell mechanical interactions. Under impaired ERK activity during bacterial infection, the simulations reproduce reduced extrusion efficiency (observed in vitro) and demonstrate that the loss of cell polarization weakens force transmission between cells, as shown in vitro. Equalizing the stiffness of infected and uninfected cells further diminishes cell mechanical competition, while reduced cell contractility leads to more infection spread. Additionally, more rounded infection domains enhance mechanical competition by promoting greater extrusion of infected cells compared to more irregular domains. These in silico results where then confirmed in vitro. Overall, this work demonstrates that computational models provide a powerful framework for unravelling the mechanical principles that govern infection induced cell competition and enable the systematic exploration of mechanotransduction mechanisms that are difficult to isolate experimentally.

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