Abstract Number: PB0734
Meeting: ISTH 2020 Congress
Background: Fibrinogen is a key mechanical protein in blood coagulation since it is the building block of fibrin fibers, and these 100 nm thick fibers provide mechanical and structural stability to blood clots as they stem the flow of blood. Fibrinogen has two large, intrinsically unfolded regions, termed alphaC regions, which comprise 27% of its molecular weight. The role of these unfolded regions has long puzzled scientists.
Aims: We aim to determine if the αC region contributes significantly to the mechanical properties of fibrin fibers, and if so, which part of the αC region it is.
Methods: We used a nano-mechanical manipulation method, based on a combined atomic force and optical microscope, to determine the mechanical properties of native fibrin fibers, and of fibers formed from fibrinogen variant AαΔ1-10. In this variant, amino acids α264-391 in the aC connector region, which consists of ten, 13-amino acid repeat segments, are deleted.
Results: Compared to native fibrin fibers, fibers formed from the variant showed dramatically different mechanical properties. The extensibility (fracture strain) was reduced by a factor of 1.6 (from 1.96 to 1.26); the fracture stress was reduced by a factor of 22 (from 13.7 MPa to 0.61 MPa); and the modulus (stiffness) decreased by a factor of 5.8 (from 6.11 MPa to 1.05 MPa).
Conclusions: The large, intrinsically unfolded αC region of fibrinogen (specifically α264-391) is a major contributor to the mechanical strength of fibrin fibers, and thus to the strength of blood clots. It suggests that the αC region has a major role in fibrin fiber assembly.
To cite this abstract in AMA style:Daraei A, Hudson N, Dement T, Guthold M. The Fibrinogen αC Region Is a Major Contributor to the Mechanical Strength of Fibrin Fibers [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-fibrinogen-%ce%b1c-region-is-a-major-contributor-to-the-mechanical-strength-of-fibrin-fibers/. Accessed September 29, 2023.
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