Planar aggregation of the influenza viral fusion peptide alters membrane structure and promotes poration

Formation of antiparallel FP dimers is highly favorable, driven primarily by peptide-peptide contacts, and not strongly influenced by membrane composition Higher order clustering of FP is membrane dependent: Cholesterol presence favors large aggregates with little lipid separating dimers In POPC, interfaces separated by a single lipid layer are also favorable In all systems, POPC is enriched around FP Lipid composition under peptide aggregates is influenced by spontaneous curvature generation of lipids: Lipids that generate negative spontaneous curvature are enriched OPC (generates positive spontaneous curvature) is depleted Enrichment of chol or DOG under FP may generate negative curvature, stabilizing tetramer formation Hypothesize that a single layer of lipids between adjacent peptides destabilizes the bilayer, facilitating poration -potentially explaining why cholesterol inhibits poration