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

Abstract

Fibrin gels are biological networks that play a fundamental role in blood coagulation and other patho/physiological processes, such as thrombosis and cancer. Electron and confocal microscopies show a collection of fibers that are relatively monodisperse in diameter, not uniformly distributed, and connected at nodal points with a branching order of~3-4. Although in the confocal images the hydrated fibers appear to be quite straight (mass fractal dimension D m ¼ 1), for the overall system 1<D m <2. Based on the confocal images, we developed a method to generate three-dimensional (3D) in silico gels made of cylindrical sticks of diameter d, density r, and average length hLi, joined at randomly distributed nodal points. The resulting 3D network strikingly resembles real fibrin gels and can be sketched as an assembly of densely packed fractal blobs, i.e., regions of 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 a factor h ¼ x/x 0 and have D m~1 .2-1.6. The in silico gels' structure is quantitatively analyzed by its 3D spatial correlation function g 3D (r) and corresponding power spectrum I(q) ¼ FFT 3D [g 3D (r)], from which r, d, D m , h, and x 0 can be extracted. In particular, x 0 provides an excellent estimate of the gel mesh size. The in silico gels' I(q) compares quite well with real gels' elastic light-scattering measurements. We then derived an analytical form factor for accurately fitting the scattering data, which allowed us to directly recover the gels' structural parameters.