Role of Pore Forming Toxins in Modulating the Lipid Dynamics

Abstract

Pore forming toxins (PFT's) are important bacterial virulence factors secreted by bacteria and pathogens. These are water-soluble monomers that spontaneously oligomerize and form self-assembled structures on the host membrane cell, intake nutrition, inhibit the activity ultimately causing cell lysis and cell death. In this study, we investigate the influence of PFT's on the dynamics of two mammalian cell membranes (DMPC and DOPC) in the presence of cholesterol. We show that cholesterol fluidizes the membrane accelerating the dynamics. In the absence of cholesterol, the lipids form crystallized lipid-protein complexes causing a slowdown in dynamics in the vicinity of the protein. We also found that the dynamics of lipids is strongly coupled to their local structure and also on the nature of lipid-protein interactions. The lipid-protein interactions are influenced by the dominant structure of the transmembrane protein in the lipid bilayer and hence depends on the type of the PFT. There exists structural and dynamical heterogeneities in the lipid bilayer and in each leaflet very similar to fluids approaching glass transition. We show that the upper leaflet from where the toxin inserts into the membrane exhibits a slower dynamics than the bottom leaflet and the alpha-PFT perturbs the membrane to a greater extent than the beta-PFT. This study will shed light on the toxicity level of the PFT in influencing the lipid dynamics and the role of cholesterol on lipid-protein interactions.