Nanostructure of the Fibrin Clot

Abstract

The nanostructure of the fibrin fibers in fibrin clots is investigated by using spectrometry and small angle x-ray scattering measurements. First, an autocoherent analysis of the visible light spectra transmitted through formed clots is demonstrated to provide robust measurements of both the radius and density of the fibrin fibers. This method is validated via comparison with existing small-angle and dynamic light-scattering data. The complementary use of small angle x-ray scattering spectra and light spectrometry unambiguously shows the disjointed nature of the fibrin fibers. Indeed, under quasiphysiological conditions, the fibers are approximately one-half as dense as their crystalline fiber counterparts. Further, although the fibers are locally crystalline, they appear to possess a lateral fractal structure.

The clinical relevance of altered fibrinogen packaging in the presence of 17β-estradiol and progesterone

“…It contain three pairs of polypeptide chains (Aα, Bβ and γ polypeptides) which are curved into a central E-region with two distal D-regions [43,44] (see Figure 8). Fibrinogen orientation is influenced by fibrinogen concentration [45,46] as well as the surface charge [47].…”

Fibrin structural and diffusional analysis suggests that fibers are permeable to solute transport

“…Thrombin (factor IIa), a protease, cleaves the fibrinopeptides A and B from the fibrinogen molecule resulting in fibrin monomers that spontaneously polymerize once they are formed [15]. Fibrin hydrogels exhibit a fibrous structure which has been the subject of many studies [16][17][18][19] and encompasses a range of scales, as illustrated in Fig. 1.…”

“…Ionic strength [18], specifically the concentrations of calcium [21] and chloride ions [22] also have an effect on structure. Finally, changes in factor XIIIa concentration have been shown to affect the packing of protofibrils within the fibers, with higher concentrations of factor XIIIa leading to fibers with a smaller distance between the constituent protofibrils [23].…”

“…In the case of fibrin, water exists not only in the space between fibers but also within the individual fibers that constitute the hydrogel. It has been estimated that only a small part of the actual fiber volume, between 10 and 30 vol %, is occupied by the protein with the rest being taken up by water [18,27,28]. Several studies have focused on unraveling the details of the internal fiber structure, showing that it is strongly influenced by the concentrations of fibrinogen and thrombin as well as the ionic strength during polymerization [17,18,27].…”

“…Starting from the assumption that the hydrogel consists entirely of an isotropic collection of rigid rods, turbidimetry relates changes in optical absorbance over a range of wavelengths with the diameter and mass-length ratio of the fibers. However, the analysis critically relies on several assumptions to relate light scattering to hydrogel structural properties as these are not directly observed, and literature findings until now have mainly been limited to hydrogels of rather low fibrinogen concentrations (less than 2 mg/mL) [18,19,30]. Confocal microscopy has mainly been used to quantify pore sizes in fibrin hydrogels [31,32].…”