After this description of native coagulation, we provide an overview of currently available procoagulant hemostatic therapies, sealants and adhesives for topical and systemic clinical use in humans. We summarize what is known about fibrin clots from a soft mechanics perspective and describe how molecular features of fibrin give rise to emergent mechanical properties at the network level that are well adapted to the physiological role of fibrin in stopping fluid flow. We highlight single-molecule biophysical studies on proteins involved in coagulation, with an emphasis on structure and conformation-based mechanisms. We begin by summarizing our current understanding of the cellular and molecular events taking place during primary and secondary hemostasis. This review provides a current perspective on engineered coagulation therapies with a particular emphasis on molecular, structural and biophysical properties of fibrin. Given the importance of coagulation and its role in a broad range of pathological conditions, the development of engineered biological therapeutics targeting fibrin and the coagulation system is of high interest in molecular biosciences. 2021) furthermore demonstrates the importance of coagulation physiology in the treatment and prevention of transmissible diseases. 2020) as well as vaccine recipients (Schultz et al. Dysregulation of coagulation in COVID-19 patients (Helms et al. In light of recent clinical and molecular physiological studies on proteins involved in the coagulation cascade, the classical model of the intrinsic and extrinsic coagulation pathways is being evaluated more closely. These signals must maintain a delicate balance in order to achieve appropriate hemostasis, being capable of rapidly stopping excessive bleeding or rebleeding events following trauma, while simultaneously avoiding unwanted, disseminated or prolonged thrombus formation. The multicomponent coagulation system is regulated by an interplay of prothrombotic and antithrombotic signals in the blood. 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.
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. In this topical review, we summarize our current understanding of the coagulation cascade from a molecular, structural and biophysical perspective. Based on its clinical importance, fibrin is being investigated as a potentially valuable molecular target in the development of coagulation therapies. 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. 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.
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The coagulation cascade represents a sophisticated and highly choreographed series of molecular events taking place in the blood with important clinical implications.
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