Lysenin Induced Membrane Curvature on Erythrocytes and Nanoporous Mica Free Standing Membranes

Abstract

Beta porin toxins are virulence factors that oligomerize in host cell membranes, forming beta-barrel pores that permeabilize target cells, leading to osmotic imbalance, cell lysis, and immune evasion. Despite extensive research on beta-pore-forming toxins (PFTs), significant gaps remain in understanding their role as actors of large-scale supramolecular membrane remodeling. While beta-PFTs are traditionally viewed as passive cylindrical conduits, their biological efficacy is fundamentally tied to an evolved ability to structurally alter the host cell membrane. In this study, we combine erythrocytes, model membranes and a novel engineered nanopores on mica substrates. We overcome the limitation of traditional mica substrates and demonstrate that lysenin pores do not merely permeabilize the membrane; they curve it into rigid, dome-like supramolecular structures. Moreover, to gain biophysical insight beyond the standard membrane models which do not directly consider the membrane insertions, we propose a hybrid model combining the biophysical models and the architectural models of pendentive domes, where the intrinsic wedge-shaped geometry of the monomers is considered. Experimental mechanical assessment of the lysenins domes shows a non-linear mechanical of stiffness with respect the radius of curvature as predicted by our hybrid model. Collectively, our work suggests that the beta-PFTs induce membrane curvature by the assembly of wedges. Beyond their pore-forming function, this membrane-bending activity may represent an additional mechanism by which beta-PFTs interfere with host-cell membrane repair.