Environmental Control of Amyloid Polymorphism by Modulation of Hydrodynamic Stress

The phenomenon of amyloid polymorphism is a keyfeature of protein aggregation. Unravelling this phenomenon is of greatsignificance for understanding the underlying molecular mechanismsassociated with neurodegenerative diseases and for the development ofamyloid-based functional biomaterials. However, the understanding ofthe molecular origins and the physicochemical factors modulatingamyloid polymorphs remains challenging. Herein, we demonstrate anassociation between amyloid polymorphism and environmental stressin solution, induced by an air/water interface in motion. Our resultsreveal that low-stress environments produce heterogeneous amyloidpolymorphs, including twisted, helical, and rod-likefibrils, whereashigh-stress conditions generate only homogeneous rod-likefibrils.Moreover, high environmental stress converts twistedfibrils into rod-likefibrils both in-pathway and after the completion of mature amyloid formation. These results enrich our understanding ofthe environmental origin of polymorphism of pathological amyloids and shed light on the potential of environmentallycontrolled fabrication of homogeneous amyloid biomaterials for biotechnological applications.