(596j) Effect of Fibril Alignment On Macromolecule Diffusion in Fibrin Gels

Fibrin-containing blood clots experience substantial strain due to platelet contraction, fluid shear, and mechanical stress at the wound site. Recently, we and others [Adhikari et al., Biomacromolecules (2012); Varju et al., J. Thromb. Haemostasis (2011)] reported that strain protects fibrin clots from proteolysis, and moreover leads to marked decreases in macromolecular diffusivity perpendicular to the strain axis. In this work, we examine the physical origins of strain-induced diffusional anisotropy in fibrin networks. We use confocal fluorescence recovery after photobleaching (FRAP) to measure macromolecular diffusivities in fibrin clots of varying density and fibril alignment. We then present analytical theory and modeling that account for the pronounced diffusional anisotropy that is observed in response to fibril alignment. The resulting model is potentially medically significant, given that the diffusion of proteolytic factors into clots is essential during the treatment of a myocardial infarct (heart attack) and deep vein thrombosis.  In addition, anisotropic diffusion in strained tissues may play presently unrecognized roles in guiding embryonic development and tissue regeneration.