Unraveling the Link between Nonlinear Mechanics, Microstructure, and Molecular Packing of Fibrin

Abstract

When we cut ourselves, our body's immediate response is to stop the bleeding by repairing the damage to the wall of the blood vessel_forming a “blood clot”. This is physically carried out by forming a network of semiflexible fibrin fibers, which bind together red blood cells and platelets, thus effectively plugging the hole that results from the injury. Recent works have shown that fibrin exhibits extraordinary material properties: it can be stretched up to 5 times its original length and it can stiffen more than 100 fold in the process. Unraveling the biophysical mechanisms behind these phenomena not only can help us better understand how our body maintains haemostasis, but also can provide useful design principles for (bio)materials.In this work, we relate the nanoscale polymerization kinetics to the microscale fiber and network structure, and to the macroscale rheological properties of fibrin. We identified distinct temporal stages in which fibrils aggregate laterally to form floppy fibers, followed by slow compaction of the fibril bundles. Furthermore, we show a direct correlation between the slow formation of high-molecular-weight chain oligomers with a slow decrease in fiber diameter and a concomitant slow increase in clot stiffness. A comparison with theoretical model of bundled semiflexible polymer networks reveals that cross-linking enhances the tightness of coupling between protofibrils within fibers. This compaction leads to the stiffening of fibers, and thus underlies the stiffening of clots. Strikingly, the stiffening effect becomes negligible when the samples are subjected to a large mechanical deformation, suggesting that the mechanics of highly stressed clots is governed by intrinsic fibril stretching. Together, our work provides a detailed biophysical picture explaining how the hierarchical structure of fibrin is interconnected with its formation and mechanics at multiple length-scales.