Structure of fibrin gels studied by elastic light scattering techniques: Dependence of fractal dimension, gel crossover length, fiber diameter, and fiber density on monomer concentration

Abstract

The concentration dependence of the structure of fibrin gels, formed following fibrinogen activation by thrombin at a constant molar ratio, was investigated by means of elastic light scattering techniques. The scattered intensity distributions were measured in absolute units over a wave-vector range q of about three decades ( approximately 3x10(2)-3x10(5) cm(-1)). A set of gel-characterizing parameters were recovered by accurately fitting the data with a single function recently developed by us [F. Ferri et al., Phys. Rev. E 63, 031401 (2001)], based on a simple structural model. Accordingly, the gels can be described as random networks of fibers of average diameter d and density rho, entangled together to form densely packed and spatially correlated blobs of mass fractal dimension D(m) and average size (or crossover length) xi. As previously done for d, we show here that the recovered xi is also a good approximation of a weight average, namely, d approximately sqrt[<d2>(w)] and xi approximately <xi>(w). By varying the fibrinogen concentration c(F) between 0.034-0.81 mg/ml, gels with 100> or =xi> or =10 microm, 100< or =d< or =200 nm, 1.2< or =D(m)< or =1.4, and constant rho approximately 0.4 mg/ml were obtained. The power-law c(F) dependencies that we found for both xi and d are consistent with the model, provided that the blobs are allowed to partially overlap by a factor eta likewise scaling with c(F) (2> or =eta> or =1). Recasting the whole dataset on a single master curve provided further evidence of the similarity between the structures of all the gels, and confirmed the self-consistency of the model.

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

“…Fibrinogen is a large centrosymmetric glycoprotein [41,42]. 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).…”

Modeling of Fibrin Gels Based on Confocal Microscopy and Light-Scattering Data

“…To do that, we sliced the 3D FIGURE 2 (a) 3D rendering of a real fibrin gel obtained from confocal microscopy images. The gel was prepared at a fibrinogen concentration c F ¼ 0.5 mg/ml, as in Ferri et al (23). (b) The same rendering for an in silico gel obtained as described in the text.…”

“…The resulting 3D network bears a striking resemblance to that of real fibrin gels and, when quantitatively analyzed by means of its 3D spatial correlation function g 3D (r) and corresponding power spectrum I(q) ¼ FFT 3D [ g 3D (r)], it exhibits a fractal morphology with D m close to that of actual fibrin gels and a spatial structure ordered on length scales comparable to the average length of the gel fibers. Based on these results, we were able to describe the gel as an assembly of densely packed fractal blobs (see Ferri et al (22,23) and references therein), i.e., regions of mass fractal dimension D m and size x where the fiber concentration is higher than average. The blobs are placed at a distance x 0 between their centers of mass so that they are overlapped by factor h ¼ x/x 0 .…”

“…The common feature of all of these models is that they are validated by comparing mainly their mechanical properties with those of the real network they aim to reproduce, and very little attention is paid to the agreement between the static and structural/morphological properties of the real gel versus those of the in silico network. In this work, we followed the complementary approach of developing a method for generating 3D in silico networks that is focused on matching the static structural properties with those of real fibrin gels as revealed by confocal microscopy and elastic light scattering (ELS) measurements (22)(23)(24).…”

“…However, electron microscopy determinations have constrained the branching order to~3-4 (27). At the same time, ELS data show that the gel structure exhibits a fractal morphology, with a mass fractal dimension 1<D m <2, and is characterized by a long-range spatial order whose length scale is comparable to the gel mesh size (22)(23)(24). Taking into account these structural features, we implemented a simple iterative algorithm that allows one to generate in silico gels as an assembly of cylindrical sticks of equal diameter d, joined together at randomly distributed nodal points.…”