E. O. Vasilenko

SARS-CoV-2 viral entry requires membrane fusion, facilitated by fusion peptides within its spike protein. While these predominantly hydrophobic peptides insert into target membranes, their precise mechanistic role in membrane fusion remains incompletely understood. Here, we investigate how FP1, the N-terminal fusion peptide sequence, modulates membrane stability and barrier function across various model membrane systems. Through a complementary suite of biophysical techniques—including electrophysiology, fluorescence spectroscopy, and atomic force microscopy—we demonstrate that FP1 significantly promotes pore formation and alters membrane mechanical properties. Our findings reveal that FP1 reduces the energy barrier for membrane defect formation and stimulates the appearance of stable conducting pores, with effects modulated by membrane composition and mechanical stress. The observed membrane-destabilizing activity suggests that beyond its anchoring function, FP1 may facilitate viral fusion by locally disrupting membrane integrity. These results provide mechanistic insights into SARS-CoV-2 membrane fusion mechanisms and highlight the complex interplay between fusion peptides and target membranes during viral entry.

The development of many neurodegenerative diseases is associated with the formation of pathological protein aggregates. In some cases, these aggregates can be formed by multilayer adsorption of ligands on a matrix, for example, the set of membrane protein receptors. The paper proposes a thermodynamic model describing the formation of linear aggregates in which ligands can be stacked. The cases when these stacks consist of complexes of one or two different types are considered. The developed model can be applied to the study of pathological aggregation of proteins of different nature, primarily beta-amyloid and its isoforms. The mean, variance and entropy of the theoretical distributions of aggregate sizes are calculated. A comparison with other theoretical models of the formation of amyloid aggregates is made.

The formation of pathological protein aggregates is associated with many neurodegenerative diseases. The aggregates can form by multilayer adsorption of ligands on a matrix in some cases; for example, the set of membrane protein receptors may act as a matrix. A thermodynamic model was developed to describe the formation of linear aggregates in which ligands are stacked. Cases where complexes of the same type or two different types form the stacks are considered. The model can be used to study pathological aggregation of various proteins and, primarily, amyloid β and its isoforms. The mean, variance, and entropy were calculated for a theoretical distributions of aggregate sizes. A comparison was made with other theoretical models of the formation of amyloid aggregates.