Biology subjects

Martin Gonzalez, N.

Publications and source records attributed to Martin Gonzalez, N..

2 recordsLinked to original sources

bioRxiv2026

Stepwise assembly and mechanical stability of nsP3 Helical Scaffolds in Chikungunya Virus

Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus that replicates its genome through a viral replication complex (RC) essential for successful infection. The RC consists of four non-structural proteins: nsP1, nsP2, nsP3, and nsP4. In this study, we focused on nsP3, which comprises three distinct domains: the alphavirus unique domain (AUD), the long and intrinsically disordered hypervariable domain (HVD), and the enzymatic macrodomain (MD). Notably, nsP3 assembles into helicoidal macrostructures, termed helical scaffolds (HSs), which are components of the CHIKV replication complex and are involved in the formation of macromolecular traps in the cytoplasm of the infected cell called Alphagranules (AGs). HSs form tubular helical scaffolds assembled through the AUD, with the MD and HVD flexibly deployed to the scaffold exterior. Despite their functional importance, the mechanisms governing HS formation remain poorly understood. Using High-Speed Atomic Force Microscopy (HS-AFM) and Electron Microscopy (EM) we achieved new findings on the structure, mechanics and assembly of these macrostructures. Our results show the nsP3 monomers follow intermediate steps before completing the assembly into full helical scaffolds, with each nsP3 domain contributing differently to this process. The macrodomain (MD) provides mechanical stability, yet it fractures under tens of piconewtons of force. This rigidity acts as a mechanical regulator that constrains the position of the HVD, which in turn mediates interactions with host factors and neighboring HSs. Through this interplay, nsP3 achieves both structural cohesion and functional adaptability, promoting the higher-order organization of HSs into honeycomb-like networks.

molecular biology↗

bioRxiv2026

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

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.

biophysics↗