Molecular Creep Induced Fatigue Rupture of Fibrin Clots

Fibrin networks, the structural framework of thrombi, undergo fatigue failure under pulsatile blood flow, posing risks of embolic events like stroke, pulmonary embolism. While fibrin's fracture behavior under monotonic loading has been intensively explored, its fatigue mechanism that governs thrombus embolization is understudied. Multiscale experiments, modeling of condensed fibrin networks, reveal a paradoxically low fatigue threshold despite high fracture energy. Mechanistically, cyclic loading induces irreversible α-to-β transitions in fibrin's molecular chains, causing molecular creep that dissipates strain energy, propagates cracks via rupture of stress-localized fibers. A multiscale continuum model quantitatively links this nanoscale mechanics to macroscale fatigue, providing an alternative mechanism of thrombus rupture as a molecular disorder driven by cumulative conformational damage. These findings reexamine widely adopted fibrous hydrogel design paradigms while bridging molecular structure characteristics to clinical thrombosis-a critical step toward predictive rupture risk assessment, targeted therapeutic strategies.