title: Mechanism of fibrin(ogen) forced unfolding.
abstract: Fibrinogen, upon enzymatic conversion to monomeric fibrin, provides the building blocks for fibrin polymer, the scaffold of blood clots and thrombi. Little has been known about the force-induced unfolding of fibrin(ogen), even though it is the foundation for the mechanical and rheological properties of fibrin, which are essential for hemostasis. We determined mechanisms and mapped the free energy landscape of the elongation of fibrin(ogen) monomers and oligomers through combined experimental and theoretical studies of the nanomechanical properties of fibrin(ogen), using atomic force microscopy-based single-molecule unfolding and simulations in the experimentally relevant timescale. We have found that mechanical unraveling of fibrin(ogen) is determined by the combined molecular transitions that couple stepwise unfolding of the γ chain nodules and reversible extension-contraction of the α-helical coiled-coil connectors. These findings provide important characteristics of the fibrin(ogen) nanomechanics necessary to understand the molecular origins of fibrin viscoelasticity at the fiber and whole clot levels.
authors.affiliation: Department of Chemistry, University of Massachusetts, Lowell, MA 01854, USA.
authors.forename: Artem
authors.initials: A
authors.lastname: Zhmurov
authors.forename: Andre E X
authors.initials: AE
authors.lastname: Brown
authors.forename: Rustem I
authors.initials: RI
authors.lastname: Litvinov
authors.forename: Ruxandra I
authors.initials: RI
authors.lastname: Dima
authors.forename: John W
authors.initials: JW
authors.lastname: Weisel
authors.forename: Valeri
authors.initials: V
authors.lastname: Barsegov
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D013816:Thermodynamics
chemical_list: D005340:Fibrinogen
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