Deconstructing fibrin(ogen) structure.

Abstract

Fibrinogen and its insoluble degradation product fibrin are pivotal plasma proteins that play important roles in blood coagulation, wound healing, and immune responses. This review highlights research from the last 24 months connecting our progressing view of fibrin(ogen)'s structure, and in particular its conformational flexibility and post-translational modifications (PTMs), to its (patho)physiological roles, molecular interactions, mechanical properties, use as a biomaterial, and potential as a therapeutic target. Recent work suggests that fibrinogen structure is highly dynamic, sampling multiple conformations, which may explain its myriad physiological functions and the presence of cryptic binding sites. Investigations into fibrin clot structure elucidated the impact of PTMs, therapeutic interventions, and pathological conditions on fibrin network morphology, offering insights into thrombus formation and embolization. Studies exploring the mechanical properties of fibrin reveal its response to blood flow and platelet-driven contraction, offering implications for clot stability and embolization risk. Moreover, advancements in tissue engineering leverage fibrin's biocompatibility and customizable properties for diverse applications, from wound healing to tissue regeneration and biomaterial interactions. These findings underscore the structural origins of fibrin(ogen)'s multifaceted roles and its potential as a target for therapeutic interventions.