The Mechanical Mechanism of Platelet Induced Clot Stiffening

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The mechanical properties of blood clots are important to properly stem the flow of blood at the site of vascular injury. A blood clot is a complex material composed of many different proteins and cells. However, particularly important for its mechanical properties, is a meshwork of the protein fibrin which serves as the structural scaffold of the clot. One important feature of fibrin network mechanics is strain-stiffening: a stiffness that is constant at low strains and increases non-linearly with strain at high strains. During blood coagulation, fibrin forms in the presence of platelets which are known to greatly influence the mechanics and structure of fibrin gels. Although both platelets and fibrin are very important to the mechanics of blood clots, the underlying principles that determine fibrin mechanics and how platelets alter these remains poorly understood. In our study, we investigate the origin of strain-stiffening in fibrin gels and how this is influenced by platelets. Using confocal microscopy subsequent image analysis, we track the 3D network structure as it undergoes shear. We find that the mechanics of the network are dictated largely by its structure. Specifically, at low strains the network utilizes soft bending modes to deform without stretching the individual fibers, while at high strains these modes are exhausted and the fibers must begin to become stretched. To understand how platelets change these properties, we polymerize fibrin gels in the presence of activated platelets. We then image the structure of the network and measure its corresponding mechanical changes. We find that the low-strain stiffness increases with increasing platelet concentration while the high-strain stiffness remains unaltered. Platelets induce aster-like structures in the fibrin gel. The altered mechanical and structural properties are consistent with platelets reducing the number of available soft bending modes.