Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Monday Speaker Abstracts

SHEAR PRIMING DECREASES ENDOTHELIAL CELLS' SUSCEPTIBILITY TO LISTERIA MONOCYTOGENES INFECTION, LIKELY DUE TO A DECREASE IN MACROPINOCYTOSIS ACTIVITY Erva Keskin 1,2 ; Aylin Balmes 3 ; Julio Cesar Sanchez-Rendon 1,2 ; Mai Wang 4 ; Tilman Schäffer 3 ; Effie Bastounis 1,2 ; 1 University of Tübingen, Interfaculty Institute of Microbiology and Infection Medicine, Cluster of Excellence "Controlling Microbes to Fight Infections" (CMFI, EXC 2124), Tübingen, Germany 2 Humboldt-University of Berlin, Institute for Biology, Berlin, Germany 3 University of Tübingen, Institute for Applied Physics, Tübingen, Germany 4 University Hospital Heidelberg, Medical Microbiology and Hygiene, Heidelberg, Germany Endothelial cells (ECs) form a protective barrier lining blood vessels, yet blood-borne pathogens such as Listeria monocytogenes (Lm) can breach this interface to cause systemic infection. While host-pathogen biochemical interactions are well studied, how mechanical forces generated by blood flow regulate endothelial susceptibility to infection remains poorly understood. We hypothesized that shear stress mechanically primes ECs by increasing cortical tension, thereby suppressing endocytic uptake pathways exploited by Lm.To test this, we applied controlled apical shear stress gradients to EC monolayers using a fluid jet device and quantified bacterial infection rate, adhesion and invasion after flow was stopped. Shear-exposed ECs exhibited a significant reduction in Lm internalization compared to monolayers never exposed to flow (static conditions). This decreased susceptibility extended to non-pathogenic Listeria innocua indicating a general suppression of passive uptake rather than pathogen-specific signaling. Atomic force microscopy (AFM) revealed a significant increase in cortical stiffness in shear-primed ECs and TFM measurements showed elevated traction stresses under flow exposure, indicating elevated membrane tension. Functionally, pharmacological inhibition or nutrient starvation-induced suppression of macropinocytosis phenocopied the shear-induced protection, significantly reducing bacterial entry under static conditions. These findings support a model in which Lm exploits macropinocytic pathways for endothelial entry that are mechanically inhibited by shear stress. Together, our results identify shear-dependent mechanical regulation of macropinocytosis as a key determinant of endothelial susceptibility to Lm infection and suggest that vascular regions experiencing disturbed or low shear stress may represent invasion hot spots.

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