MIRA R35: Fibrin(ogen) in regulating health and disease

PROJECT SUMMARY/ABSTRACT Fibrin(ogen) plays a critical role in processes such as wound healing, coagulation, cancer, pregnancy, and inflammation. Fibrin(ogen), which is a blood plasma protein, forms a hierarchical network that gives rise to its unique mechanical and enzymatic stability. There is a need to understand the interplay between changes in the biochemical microenvironment that lead to the resulting fibrin network structure and its mechanical properties. We seek to apply engineering and biophysical techniques to address these fundamental questions. The long-term goal of the laboratory is to delineate the role that the structure- function relationship of fibrin(ogen) plays in regulating health and disease. To do this we will characterize the relationship of fibrin network structure with viscoelastic and rupture mechanics. Then, we will assess the rupture resistance of fibrin-collagen composites. We will determine how these two materials behave mechanically both together and at their interface to better understand the regulation of wound healing. We will study kinetics and the enzymatic dissolution of fibrin networks, where we will probe the influence of medications on stability. These fundamental studies have important translational and diagnostic implications going forward.