Biomechanical origins of inherent tension in fibrin networks.

Blood clots form at the site of vascular injury to seal the wound and prevent bleeding. Clots are in tension as they perform their biological functions and withstand hydrodynamic forces of blood flow, vessel wall fluctuations, extravascular muscle contraction and other forces. There are several mechanisms that generate tension in a blood clot, of which the most well-known is the contraction/retraction caused by activated platelets. Here we show through experiments and modeling that clot tension is generated by the polymerization of fibrin. Our mathematical model is built on the hypothesis that the shape of fibrin monomers having two-fold symmetry and off-axis binding sites is ultimately the source of inherent tension in individual fibers and the clot. As the diameter of a fiber grows during polymerization the fibrin monomers must suffer axial twisting deformation so that they remain in register to form the half-staggered arrangement characteristic of fibrin protofibrils. This deformation results in a pre-strain that causes fiber and network tension. Our results for the pre-strain in single fibrin fibers is in agreement with experiments that measured it by cutting fibers and measuring their relaxed length. We connect the mechanics of a fiber to that of the network using the 8-chain model of polymer elasticity. By combining this with a continuum model of swellable elastomers we can compute the evolution of tension in a constrained fibrin gel. The temporal evolution and tensile stresses predicted by this model are in qualitative agreement with experimental measurements of the inherent tension of fibrin clots polymerized between two fixed rheometer plates. These experiments also revealed that increasing thrombin concentration leads to increasing internal tension in the fibrin network. Our model may be extended to account for other mechanisms that generate pre-strains in individual fibers and cause tension in three-dimensional proteinaceous polymeric networks.

Humidity dependence of fracture toughness of cellulose fibrous networks.

Cellulose-based materials are increasingly finding applications in technology due to their sustainability and biodegradability. The sensitivity of cellulose fiber networks to environmental conditions such as temperature and humidity is well known. Yet, there is an incomplete understanding of the dependence of the fracture toughness of cellulose networks on environmental conditions. In the current study, we assess the effect of moisture content on the out-of-plane (i.e., z-dir.) fracture toughness of a particular cellulose network, specifically Whatman cellulose filter paper. Experimental measurements are performed at 16% RH along the desorption isotherm and 23, 37, 50, 75% RH along the adsorption isotherm using out-of-plane tensile tests and double cantilever beam (DCB) tests. Cohesive zone modeling and finite element simulations are used to extract quantitative properties that describe the crack growth behavior. Overall, the fracture toughness of filter paper decreased with increasing humidity. Additionally, a novel model is developed to capture the high peak and sudden drop in the experimental force measurement caused by the existence of an initiation region. This model is found to be in good agreement with experimental data. The relative effect of each independent cohesive parameter is explored to better understand the cohesive zone-based humidity dependence model. The methods described here may be applied to study rupture of other fiber networks with weak bonds.

Structure, mechanical properties, and modeling of cyclically compressed pulmonary emboli.

Pulmonary embolism occurs when blood flow to a part of the lungs is blocked by a venous thrombus that has traveled from the lower limbs. Little is known about the mechanical behavior of emboli under compressive forces from the surrounding musculature and blood pressure. We measured the stress-strain responses of human pulmonary emboli under cyclic compression, and showed that emboli exhibit a hysteretic stress-strain curve. The fibrin fibers and red blood cells (RBCs) are damaged during the compression process, causing irreversible changes in the structure of the emboli. We showed using electron and confocal microscopy that bundling of fibrin fibers occurs due to compression, and damage is accumulated as more cycles are applied. The stress-strain curves depend on embolus structure, such that variations in composition give quantitatively different responses. Emboli with a high fibrin component demonstrate higher normal stress compared to emboli that have a high RBC component. We compared the compression response of emboli to that of whole blood clots containing various volume fractions of RBCs, and found that RBCs rupture at a certain critical stress. We describe the hysteretic response characteristic of foams, using a model of phase transitions in which the compressed foam is segregated into coexisting rarefied and densified phases whose fractions change during compression. Our model takes account of the rupture of RBCs in the compressed emboli and stresses due to fluid flow through their small pores. Our results can help in classifying emboli as rich in fibrin or rich in red blood cells, and can help in understanding what responses to expect when stresses are applied to thrombi in vivo.