We have described how lipid membranes affect formation of transmembrane pores in lipid membranes. We published this in an excellent journal from the field of chemistry. We have described, also based on some of our published results, that lipid membranes affect binding of proteins to lipid membranes, their oligomerization and insertion in the membranes in order to form transnembrane pores.
The invertebrate cytolysin lysenin is a member of the aerolysin family of membrane pore-forming toxins that includes many representatives from pathogenic bacteria. In this study, we determined the crystal structure of the lysenin pore and thereby for the first time provided insights into its assembly mechanism. The lysenin pore is assembled from nine monomers via dramatic reorganization of almost half of the monomeric subunit structure leading to a β-barrel pore ∼10 nm long and 1.6-2.5 nm wide. The lysenin pore is devoid of additional luminal compartments as commonly found in other toxin pores. Mutagenic analysis and atomic force microscopy imaging, together with these structural insights, suggested a mechanism for pore assembly for lysenin. These insights are relevant to the understanding of pore formation by other aerolysin-like pore-forming toxins, which often represent crucial virulence factors in bacteria.
We have used HS-AFM approach to show how listeriolysin O damage lipid membranes. We have realised that listeriolysin O form incomplete rings (arcs) at the surface of the lipid membrane. The damage of lipid membranes involves also merging of arcs into larger assemblies, which form bigger lesions that could also allow escape of bacteria in the context of phagocytic membranes.
We have shown tha listeriolysin O form pores at different pH values. This is physiologically important. We have also shown that pH affects the pore formation. In addition pores can fuse to larger oligomeric complexes.
Extracellular vesicles (EVs) are membrane vesicles that are produced by cells to be released into their microenvironment. EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type-specific signatures, EVs have been proposed as biomarkers in a variety of diseases.Besides, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. The rapidly emerging field of EVs will significantly influence the biomedicinal landscape in the future. In this review, the high potential of EVs for both diagnostic and therapeutic areas of nanomedicine is presented.