Polymorphism on the interfacial adhesion of amyloid-like fibrils: insights from assembly units and secondary...

Amyloid-like fibrils are closely associated with neurodegenerative diseases and play a key role in biofilm structures that have adhesion to various surfaces. Yet, the molecular origins responsible for interfacial adhesion of polymorph amyloid structures are still elusive. Here, we investigate how assembly units and structural polymorphism influence the adhesion properties of amyloid aggregates. Using lysozyme as a model protein, we engineered two types of amyloid fibrils through distinct methods. Peptide fragment amyloid fibrils (PFAF) were produced by hydrolyzing lysozyme into short peptide fragments, forming rigid, long, straight fibrils with higher β-sheet content. Full-length amyloid fibrils (FLAF) were generated by reducing disulfide bonds to expose hydrophobic cores, yielding filament fibrils with enhanced viscoelasticity. Our comparative analyses reveal that PFAF exhibits β-sheet dominant structures with high rigidity but lower adhesion forces, while FLAF demonstrates a unique combination of α-helix and disordered structures with β-sheets, resulting in superior adhesion and stability. Our findings highlight the critical roles of α-helical and disordered regions in interfacial adhesion, while the amyloidogenic β-sheet core contributes primarily to mechanical strength. This study offers a generalized framework for understanding protein-based adhesion and guiding the design of bioinspired adhesive materials.