Blood clots are essential biomaterials that prevent blood loss and provide a temporary scaffold for tissue repair. In their function, these materials must be capable of resisting mechanical forces from hemodynamic shear and contractile tension without rupture. Fibrin networks, the primary load-bearing element in blood clots, have unique nonlinear mechanical properties resulting from fibrin's hierarchical structure. This structure provides multiscale load bearing from fiber deformation to protein unfolding. Here, we study the fiber and molecular scale response of fibrin under shear and tensile loads in situ using a combination of fluorescence and vibrational (molecular) microscopy. Imaging protein fiber orientation and molecular vibrations, we find that fiber alignment and molecular unfolding in fibrin appear at much larger strains under shear compared to uniaxial tension. Alignment levels reached at 150% shear strain were reached already at 60% tensile strain, and molecular unfolding of fibrin was only detected at shear strains above 300%, whereas fibrin unfolding began already at 20% tensile strain. Moreover, shear deformation caused progressive changes in vibrational modes consistent with increased protofibril and fiber packing that were already present even at very low tensile deformation. Together with a bioinformatic analysis of the primary fibrinogen structure, we propose a scheme for the molecular response of fibrin from low to high deformation, which may relate to the teleological origin of fibrin's resistance to shear and tensile forces.
Keywords: CARS; Chemical imaging; Fibrin; Mechanical deformation; Molecular structure; Structural characterization.
Copyright © 2020. Published by Elsevier Ltd.