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Loading causes molecular damage in fibrin fibers

Norouzi, S.; Lohr, M. J.; Mohamed, M. I.; Jennings, C. M.; Wang, D.; Ren, P.; Rausch, M. K.; Parekh, S. H.

2025-05-09 biophysics
10.1101/2025.05.08.652948 bioRxiv
Show abstract

Blood clotting is the bodys natural reaction in wound healing and is also the cause of many pathologies. Fibrin - the main protein in the clotting process provides clots mechanical strength by forming a scaffold of complex fibrin fibers. Fibrin fibers exhibit high extensibility and primarily elastic properties under static loading, which differ from in vivo dynamic forces. In many biological materials, the mechanical response changes under repeated loading/unloading (cyclic loading). Using lateral force microscopy, we show fibrin fibers possess viscoelastic behavior and experience irreversible damage under cyclic loading. Cross-linking results in a more rigid structure with permanent damage occurring mostly at larger strains, which is corroborated by computational modeling of fibrin extension using a hyperelastic model. Molecular spectroscopy analysis with broadband coherent anti-Stokes Raman scattering spectroscopy in addition to molecular dynamic simulations allow identification of the source of damage, the unfolding pattern, and inter and intramolecular changes in fibrin. The results show partial recovery of proteins secondary and tertiary structures under load, providing deeper understanding of fibrins unique behavior in wound healing or pathologies like stroke and embolism.

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