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dc.contributor.author
Urosev, Ivan
dc.contributor.author
Lopez Morales, Joanan
dc.contributor.author
Nash, Michael A.
dc.date.accessioned
2020-12-21T17:09:28Z
dc.date.available
2020-10-01T07:12:00Z
dc.date.available
2020-10-02T05:30:29Z
dc.date.available
2020-12-21T17:09:28Z
dc.date.issued
2020-12-15
dc.identifier.issn
1616-3028
dc.identifier.issn
1616-301X
dc.identifier.other
10.1002/adfm.202005245
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/443778
dc.identifier.doi
10.3929/ethz-b-000443778
dc.description.abstract
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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
clotting
en_US
dc.subject
coagulation
en_US
dc.subject
hydrogel mechanics
en_US
dc.subject
protein engineering
en_US
dc.subject
rheology
en_US
dc.title
Phase Separation of Intrinsically Disordered Protein Polymers Mechanically Stiffens Fibrin Clots
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2020-09-16
ethz.journal.title
Advanced Functional Materials
ethz.journal.volume
30
en_US
ethz.journal.issue
51
en_US
ethz.journal.abbreviated
Adv. Funct. Mater.
ethz.pages.start
2005245
en_US
ethz.size
10 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Weinheim
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09586 - Nash, Michael / Nash, Michael
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09586 - Nash, Michael / Nash, Michael
ethz.date.deposited
2020-10-01T07:12:09Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-12-21T17:09:37Z
ethz.rosetta.lastUpdated
2022-03-29T04:38:47Z
ethz.rosetta.versionExported
true
ethz.COinS
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