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Fibrinogen αC-Connector is Critical for Fibrin Fiber Assembly and Mechanical Strength

A. Daraei1, T. Dement2, H. Belcher2, N. Hudson2, M. Guthold3

1UCLA, Winston-Salem, North Carolina, United States, 2East Carolina University, Greenville, North Carolina, United States, 3Wake Forest University, Winston Salem, North Carolina, United States

Abstract Number: OC 29.3

Meeting: ISTH 2022 Congress

Theme: Fibrinolysis and Proteolysis » Fibrinogen and Factor XIII

Background: Fibrinogen has two large αC regions (alpha221–610) that consists of the unstructured, 60 nm long αC-connector (α221–391) and the folded αC-domain (392–610). The unfolded αC-connector contains ten repeat segments, each consisting of 13 amino acids, running from α264-391.

Aims: Investigate the role of the αC-connector in fibrin fiber assembly and mechanical strength.

Methods: Using a transient fibrinogen expression system, we obtained variant Aα∆1-10, in which all ten repeat units are deleted. We used SEM imaging and AFM-based nanomanipulation methods, to investigate fibrin fiber morphology and mechanical properties of uncrosslinked fibers formed from variant Aα∆1-10 fibers and wild-type fibers.

Results: Fibers formed from the AαΔ1-10 variant showed dramatically different mechanical and morphological properties. Compared to wild type fibers, extensibility was reduced by a factor of 1.7 (from 2.1 to 1.26) and the modulus (stiffness) decreased by a factor of 3 (from 3 MPa to 1 MPa). SEM images show that AαΔ1-10 fibers often form a flat ribbon-like fiber, failing to form the round, cylindrical fibers seen in wild type fibers.

Conclusion(s): The αC-connector region of fibrinogen (specifically α264-391) plays a key role in proper fibrin fiber assembly, and it is a major contributor to the mechanical strength of fibrin fibers, and thus to the strength of blood clots.

Figure 1.

Variant and Wild-Type Fibers

To cite this abstract in AMA style:

Daraei A, Dement T, Belcher H, Hudson N, Guthold M. Fibrinogen αC-Connector is Critical for Fibrin Fiber Assembly and Mechanical Strength [abstract]. https://abstracts.isth.org/abstract/fibrinogen-%ce%b1c-connector-is-critical-for-fibrin-fiber-assembly-and-mechanical-strength/. Accessed November 30, 2023.

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