fibrillization

Fibrillization is the process by which certain macromolecules, notably proteins, assemble into elongated, filamentous aggregates called fibrils. When fibrils are formed by proteins that adopt a cross-β sheet structure they are often described as amyloid fibrils, although not all fibrillar aggregates are amyloid. Fibrillization occurs in both physiological contexts and disease, and the term is also used in materials science to describe the formation of nanofibrils from polymers or biopolymers such as cellulose or collagen.

Mechanistically, fibrillization often follows nucleation-dependent polymerization. Monomeric proteins misfold or rearrange into nuclei, which templates rapid elongation by addition of more monomers, yielding a growing fibril. This process typically shows a lag phase, a rapid growth phase, and a plateau. It can be accelerated by mutations, proteolytic processing, high concentration, certain pH or ionic conditions, agitation, and surfaces that catalyze nucleation. Seeding with preformed fibrils can bypass the lag phase and accelerate aggregation, a phenomenon relevant to prion-like spread.

Detection and implications: Amyloid fibrils are associated with several neurodegenerative diseases, including Alzheimer's, Parkinson's, and prion diseases, though fibrils also occur in normal cellular functions and in defense or storage roles in some organisms. In research and clinical settings, fibrillization is monitored by methods such as thioflavin T fluorescence, Congo red binding, and electron or atomic force microscopy; structural analysis reveals cross-β architecture. In materials science, fibrillization is exploited to produce nanofibrils that reinforce composites or form hydrogels with distinctive mechanical properties.

Regulation and intervention: cellular quality-control systems attempt to prevent pathogenic fibrillization, and therapeutic strategies aim to inhibit fibril formation, destabilize existing fibrils, or promote clearance. Understanding fibrillization contributes to both the study of disease mechanisms and the design of biomaterials.