Can single-fiber level strain change the molecular structure and metabolism of fibrin?

In response to wounding, fibrinogen assembles into a sparse isotropic gel formed by branching filaments and tetrafunctional cross-links where two filaments overlap. Fibrin gels exhibit nonlinear responses to shear and uniaxial deformation and have been studied as a model for weakly connected, subisostatic fibrous networks. When an initially isotropic fibrin gel is deformed in shear, only a small fraction of the fibers carries the mechanical load. Enzymes that covalently stabilize fibrin filaments (Factor XIIIa) or that degrade the fibrin gel (plasmin) preferentially react with filaments in gels that are strained in shear. Using a confocal microscope coupled with a rheometer, we observe the microscopic reorganization in a fibrin gel under strain. Shear strain increases the fluorescence of a subset of fibrin fibers labelled with FITC fluorophores, possibly due to the weakening of self-quenching as fibers stretch. The fluorescence increase is reversible when the strain is removed, and preliminary evidence shows that subsequent strains of the network produce different patterns of fluorescence enhancement, due to reorientation of fibers in the initial strain direction. Atomic force microscopy studies coupled to fluorescence imaging reveal a single-fiber level perspective on the network studies.