Stiffening of Individual Fibrin Fibers Equitably Distributes Strain and Strengthens Networks

Abstract

As the structural backbone of blood clots, fibrin networks carry out the mechanical task of stemming blood flow at sites of vascular injury. These networks exhibit a rich set of remarkable mechanical properties, but a detailed picture relating the microscopic mechanics of the individual fibers to the overall network properties has not been fully developed. In particular, how the high strain and failure characteristics of single fibers affect the overall strength of the network is not known. Using a combined fluorescence/atomic force microscope nanomanipulation system, we stretched 2-D fibrin networks to the point of failure, while recording the strain of individual fibers. Our results were compared to a pair of model networks: one composed of linearly responding elements and a second of nonlinear, strain-stiffening elements. We find that strain-stiffening of the individual fibers is necessary to explain the pattern of strain propagation throughout the network that we observe in our experiments. Fiber strain-stiffening acts to distribute strain more equitably within the network, reduce strain maxima, and increase network strength. Along with its physiological implications, a detailed understanding of this strengthening mechanism may lead to new design strategies for engineered polymeric materials.

The application of large amplitude oscillatory stress in a study of fully formed fibrin clots

“…This behaviour is expected given that individual fibrin fibres' strain stiffens and is highly extensible. 12,13,15 Our findings are similar to the LAOS controlled strain studies of van Kempen et al 25 that reported intra-cycle stiffening and softening during continuous application of large strain deformations to fibrin clots. However, an advantage of LAOStress measurements is that the fibrin clot is allowed to reach the steady state under a fixed level of oscillatory stress.…”

“…9 Thus, it is important to consider the effects of both the vast range and progressive increase in stress experienced by fully formed clots. Marked changes in the structure and rheological properties of the clot can arise as a consequence of shear stress through several different mechanisms including strain-stiffening of the fibrin network, 11 strain-stiffening of individual fibrin fibres, 12,13 protein unfolding of stretched fibres, 14 unfolding of fibrin monomers, 15 yielding of branching points, 16 slippage of protofibrils within fibres, 17 and breakage of individual fibrin fibres. 18,19 The propensity of the formed blood clot to macroscopically fracture may be influenced by all of the aforementioned mechanisms.…”

The molecular origins of the mechanical properties of fibrin

“…2C) (13, 29–32, 38). All three properties are characteristic of other elastomeric protein fibers such as elastin, resilin or spider silk (47–49) and suggest that, like these protein fibers, fibrin’s mechanical properties lie in the straightening of unstructured polypeptides.…”

“…These studies were the first to suggest that stress induces conformational changes within the protein monomer, attributed to either the coiled-coil or the D region of the protein. Recent studies have measured the mechanical properties of individual fibers (13, 29–32) or cylindrical fibrin clots (9). These studies showed the mechanical properties of clots depend on the mechanical properties of the individual fibrin monomers.…”

Tensile testing of individual glassy, rubbery and hydrogel electrospun polymer nanofibres to high strain using the atomic force microscope

“…18,[21][22][23][24][25] However, mechanical tests on nanofibre assemblies are dominated by the strength of interfibre junctions, the radius of curvature of the fibres and the alignment of fibres with the observed properties vastly different to the properties of individual fibres. 26,27 Appreciation of the mechanical properties of isolated electrospun polymer fibres is an emerging field.…”