Variability in Individual Native Fibrin Fiber Mechanics

Abstract

Fibrin fibers are important structural elements in blood coagulation. They form a mesh network that acts as a scaffold and imparts mechanical strength to the clot. A review of published work measuring the mechanics of fibrin fibers reveals a range of values for fiber extensibility. This study investigates fibrinogen concentration as a possible variable responsible for variability in fibrin fiber mechanics. It expands previous work to describe the modulus, strain hardening, extensibility, and the force required for fiber failure when fibers are formed with different fibrinogen concentrations. Lateral force atomic force microscopy was used to create stress-strain curves for individual nanofibers and data was obtained from fibers formed from 0.5 NIH U/ml thrombin, 55 Loewy U/ml FXIII, and 1 mg/ml or 2 mg/ml fibrinogen. Analysis of the mechanical properties showed fiber formed from 1 mg/ml fibrinogen and 2 mg/ml fibrinogen had significantly different mechanical properties. To help clarify our findings we developed two behavior profiles to describe individual fiber mechanics. The first describes a fiber with low initial modulus and high extensible, that undergoes strain hardening around 100 % strain, and has moderate strength. A majority of fibers formed with 1 mg/ml fibrinogen showed this behavior profile. The second profile describes a fiber with a high initial modulus, minimal strain hardening, high strength, and low extensibility. Most fibrin fibers formed with 2 mg/ml fibrinogen were described with this second behavior profile. In conclusion, we see a range of behaviors from fibers formed from native fibrinogen molecules but various fibrinogen concentrations. Potential differences in fiber formation is investigated with SEM. It is likely this range of behaviors also occurs in vivo. Understanding the variability in mechanical properties could contribute to a deeper understanding of pathophysiology of coagulative disorders.