Staphylococcus aureus PSMα1 amyloid structure is modulated by buffer and salt

Amyloid fibrils share a characteristic cross-β structure yet often display pronounced polymorphism, where a single protein or peptide sequence can adopt multiple distinct fibrillar architectures. Environmental factors such as buffer composition, ionic strength, and pH strongly influence amyloid assembly, modulating fibril morphology, stability, and function. In Staphylococcus aureus , phenol-soluble modulins (PSMs) are key contributors to biofilm integrity and pathogenicity, with PSMα1 forming stable fibrils that reinforce the biofilm matrix. However, the influence of the physicochemical environment on PSMα1 aggregation remains poorly defined. Here, we systematically examine how solution conditions, ionic strength, and cross-seeding modulate PSMα1 fibril formation. Our results show that variations in these parameters markedly alter aggregation kinetics, fibril morphology, hydrophobic surface exposure, and molecular organization. Distinct buffer conditions promote the emergence of different fibrillar polymorphs, reflecting the environmental sensitivity observed in disease-associated amyloids. These findings underscore the critical role of the solution environment in directing amyloid assembly pathways and suggest that environmentally driven fibril polymorphism may contribute to S. aureus biofilm stability and pathogenic behavior.