Matrix stiffness modulates infection of endothelial cells byListeria monocytogenesvia expression of cell surface vimentin

Abstract

AbstractExtracellular matrix (ECM) stiffness is one of many mechanical forces acting on mammalian adherent cells that influence cellular function. We have addressed the open question of how ECM stiffness might alter the susceptibility of host cells to infection by bacterial pathogens. We manufactured hydrogels of varying physiologically-relevant stiffness and seeded human microvascular endothelial cells (HMEC-1) on them. We then infected HMEC-1 with the bacterial pathogenListeria monocytogenes(Lm) and found that adhesion of Lm onto host cells increases monotonically with increasing matrix stiffness, an effect that requires the activity of focal adhesion kinase (FAK). We identified cell surface vimentin as a candidate surface receptor mediating stiffness-dependent adhesion of Lm to HMEC-1, and demonstrated that bacterial infection of these host cells is decreased when surface vimentin is perturbed. Our results provide the first evidence that ECM stiffness can mediate the susceptibility of host cells to bacterial infection.