Phase Separation of Intrinsically Disordered Protein Polymers Mechanically Stiffens Fibrin Clots

Urosev, Ivan and Lopez Morales, Joanan and Nash, Michael A.. (2020) Phase Separation of Intrinsically Disordered Protein Polymers Mechanically Stiffens Fibrin Clots. Advanced Functional Materials, 30 (51). p. 2005245.

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Fibrin (Fb) networks self-assemble through the coagulation cascade and serve as the structural foundation of blood clots. Following severe trauma or drug therapy, reduced integrity of Fb networks can lead to formation of clots with inadequate mechanical properties. A key feature of therapeutic interventions for hemostasis is therefore the ability to restore mechanical strength to clots formed under coagulopathic conditions. Here, an intrinsically disordered protein based on an elastin-like polypeptide (ELP) sequence is described, which specifically binds Fb and modulates its mechanical properties. Hemostatic ELPs (hELPs) are designed containing N- and C-terminal peptide tags that are selectivity recognized by human transglutaminase factor XIIIa and covalently linked into fibrin networks via the natural coagulation cascade. Phase separation of hELPs above their lower critical solution temperature leads to stiffening and rescue of clot biophysical properties under simulated conditions of dilutive coagulopathy. In addition to phase-dependent stiffening, the resulting hELP-Fb networks exhibit resistance to plasmin degradation, reduced pore sizes, and accelerated gelation rate following initiation of clotting. These results demonstrate the ability of protein-based phase separation to modulate the physical and biochemical properties of blood clots and suggest protein phase separation as a new mechanism for achieving hemostasis in clinical settings.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Synthetic Systems (Nash)
UniBasel Contributors:Nash, Michael and Lopez Morales, Joanan and Urosev, Ivan
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Mar 2021 11:47
Deposited On:16 Mar 2021 11:47

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