Engineered Molecular Therapeutics Targeting Fibrin and the Coagulation System: a Biophysical Perspective

The coagulation cascade represents a sophisticated and highly choreographed series of molecular events taking place in the blood with important clinical implications. One key player in coagulation is fibrinogen, a highly abundant soluble blood protein that is processed by thrombin proteases at wound sites, triggering self-assembly of an insoluble protein hydrogel known as a fibrin clot. By forming the key protein component of blood clots, fibrin acts as a structural biomaterial with biophysical properties well suited to its role inhibiting fluid flow and maintaining hemostasis. Based on its clinical importance, fibrin is being investigated as a potentially valuable molecular target in the development of coagulation therapies. In this topical review, we summarize our current understanding of the coagulation cascade from a molecular, structural and biophysical perspective. We highlight single-molecule studies on proteins involved in blood coagulation and report on the current state of the art in directed evolution and molecular engineering of fibrin-targeted proteins and polymers for modulating coagulation. This biophysical overview will help acclimatize newcomers to the field and catalyze interdisciplinary work in biomolecular engineering toward the development of new therapies targeting fibrin and the coagulation system.

Automated summary

The coagulation cascade is a series of molecular events in blood with clinical significance. Fibrinogen, a key player in coagulation, undergoes processing by thrombin proteases and forms insoluble fibrin clots at wound sites. Fibrin acts as a structural biomaterial, inhibiting fluid flow and maintaining hemostasis. Due to its clinical importance, fibrin is being studied as a potential molecular target for coagulation therapies. This topical review summarizes the current understanding of the coagulation cascade from a molecular, structural, and biophysical perspective and discusses the latest advancements in directed evolution and molecular engineering of fibrin-targeted proteins and polymers for coagulation modulation.