“Dirty” Fiber - “Clean” Fiber: A Theory of the Organization of Fibrin from Fibrinogen

Summary

A theory of fibrin formation is proposed in which gel fiber fabrication is coordinated by two distinct sets of complexing filaments emanating from spherical fibrinogen-derived structural subunits. The formulation is an attempt to correlate the previously reported ultramicroscopic negative-contrast images of fibrinogen and fibrin with a similar but unique spheroidal body observed during the organization of dysfibrin Seattle. This slow clotting dysfibrinogen manifested a predisposition to form aperiodic fibers when thrombic proteolysis and polymerization were curtailed by the progressively earlier application of an acid stain embedment reagent (uranyl acetate). The unstriated fibers were unevenly surrounded by the electron dense stain and manifested a “dirty” appearance. This “primordial” fiber was comprised of linear chains of (10 nm) complexed spheres with (15 nm) lateral filamentous projections. Fibrinogen Seattle consistently generated typically striated (26 nm), “clean”, or “mature” fiber gels when polymerization was allowed to proceed. The proposed role of these lateral filaments is to engage, align, and stabilize similar processes on globular subunits in adjacent linear chains of the “primordial” fiber. The behavior of the negative contrast reagent during the fibrinogen to fibrin conversion is assessed as a reflection of the distribution and orientation of polar residues. The“clean” or striated fiber is depicted as a highly fenestrated hollow cylinder with a hydrophilic interior. The model is fitted to ultrastructural studies on the progression of transamidation of fibrin by factor XIII_a.

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