Abstract
Blood clots are the body's natural biomaterials formed during wound healing, but they are also the cause of many pathologies, such as ischemic stroke. Fibrin, the main protein in clots, provides clots with mechanical strength through a network of fibrin fibers. These fibers exhibit high extensibility and primarily elastic properties under static loading conditions though little is known about single fiber mechanics under dynamic loading, as experienced in vivo. Indeed, many biological materials show distinct mechanical responses under repeated loading/unloading (cyclic loading), a prime example of which is clot embolization. Using lateral force microscopy, we show that fibrin fibers exhibit viscoelasticity and undergo irreversible molecular damage under cyclic loading. Cross-linking results in a more rigid structure with permanent damage occurring at larger strains - findings corroborated by computational modeling. Molecular spectroscopy analysis with broadband Raman scattering spectroscopy, combined with molecular dynamics simulations, allows identification of the damage source, unfolding pattern, and inter- and intramolecular changes in fibrin. The results reveal partial recovery of the protein's secondary and tertiary structures, providing a deeper understanding of fibrin's molecular wear under load and its behavior in wound healing and pathologies like stroke and embolism.