α−α Cross-Links Increase Fibrin Fiber Elasticity and Stiffness

Helms, Christine; Ariëns, Robert A. S.; Willige, Shirley Uitte de; Standeven, Kristina F.; Guthold, Martin

doi:10.1016/j.bpj.2011.11.4016

Cited by 87 publications

(107 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The major targets of FXIII(a) activity are the fibrin γ-and α-chains, and FXIII(a)-mediated crosslinking of these fibrin chains imparts critical structural and mechanical properties to the fibrin network. Compared with uncrosslinked fibers, crosslinked fibers are thinner and more elastic (37,38) and require greater force to rupture (39). Compared with uncrosslinked clots, crosslinked clots have smaller pores, increased network density, and a higher viscoelastic storage modulus (ref.…”

Section: Discussionmentioning

confidence: 99%

Factor XIII activity mediates red blood cell retention in venous thrombi

Aleman¹,

Byrnes²,

Wang³

et al. 2014

J. Clin. Invest.

173

209

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Factor XIII activity mediates red blood cell retention in venous thrombi

Aleman¹,

Byrnes²,

Wang³

et al. 2014

J. Clin. Invest.

173

209

View full text Add to dashboard Cite

“…These studies used whole clot rheology by torsion pendulum [30] and single fibre measurement by atomic microscopy [33], and showed an increase in fibre and clot stiffness of around 40% due to -chain cross-linking.…”

Section: Fibrin - Chains Cross-linkingmentioning

confidence: 99%

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

Duval

Ariëns

2017

Matrix Biology

View full text Add to dashboard Cite

ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ÔØ Å ÒÙ× Ö ÔØ A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractFibrin is an important matrix protein that provides the backbone to the blood clot, promoting tissue repair and wound healing. Its precursor fibrinogen is one of the most heterogenous proteins, with an estimated 1 million different forms due to alterations in glycosylation, oxidation, single nucleotide polymorphisms, splice variation and other variations. Furthermore, ligation by transglutamimase factor XIII (cross-linking) adds to the complexity of the fibrin network. The structure and function of the fibrin network is in part determined by this natural variation in the fibrinogen molecule, with major effects from slice variation and cross-linking. This mini-review will discuss the direct effects of fibrinogen EC and fibrinogen ' splice variation on clot structure and function and also discuss the additional role of fibrinogen ' as thrombomodulin II. Furthermore, the effects of crosslinking on clot function will be described. Splice variation and cross-linking are major determinants of the structure and function of fibrin and may therefore impact on diseases affecting bleeding, thrombosis and tissue repair.

show abstract

“…8,30,37 Studies with native fibrinogen vs the mutant (gQ398N, gQ399N, and gK406R) have revealed independent contributions coming from a-a crosslinks. 16,38 Such crosslinks play major roles in promoting clot stiffness, fiber straightening, and hindering fibrinolysis.…”

Section: Introductionmentioning

confidence: 99%

Ranking reactive glutamines in the fibrinogen αC region that are targeted by blood coagulant factor XIII

Mouapi

Bell

Smith

et al. 2016

Blood

View full text Add to dashboard Cite

Key Points• FXIIIa exhibits a preference for Q237 in crosslinking reactions within fibrinogen aC (233-425) followed by Q328 and Q366.• None of the reactive glutamines in aC 233-425 (Q237, Q328, and Q366) are required to react first before the others can crosslink.Factor XIIIa (FXIIIa) introduces covalent g-glutamyl-«-lysyl crosslinks into the blood clot network. These crosslinks involve both the g and a chains of fibrin. The C-terminal portion of the fibrin a chain extends into the aC region (210-610). Crosslinks within this region help generate a stiffer clot, which is more resistant to fibrinolysis. Fibrinogen aC (233-425) contains a binding site for FXIIIa and three glutamines Q237, Q328, and Q366 that each participate in physiological crosslinking reactions. Although these glutamines were previously identified, their reactivities toward FXIIIa have not been ranked. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry and nuclear magnetic resonance (NMR) methods were thus used to directly characterize these three glutamines and probe for sources of FXIIIa substrate specificity. Glycine ethyl ester (GEE) and ammonium chloride served as replacements for lysine. Mass spectrometry and 2D heteronuclear single quantum coherence NMR revealed that Q237 is rapidly crosslinked first by FXIIIa followed by Q366 and Q328. Both N-GEE could be crosslinked to the three glutamines in aC (233-425) with a similar order of reactivity as observed with the MALDI-TOF mass spectrometry assay. NMR studies using the single aC mutants Q237N, Q328N, and Q366N demonstrated that no glutamine is dependent on another to react first in the series. Moreover, the remaining two glutamines of each mutant were both still reactive. Further characterization of Q237, Q328, and Q366 is important because they are located in a fibrinogen region susceptible to physiological truncations and mutation. The current results suggest that these glutamines play distinct roles in fibrin crosslinking and clot architecture. (Blood. 2016;127(18):2241-2248

show abstract

α−α Cross-Links Increase Fibrin Fiber Elasticity and Stiffness

Cited by 87 publications

References 39 publications

Factor XIII activity mediates red blood cell retention in venous thrombi

Factor XIII activity mediates red blood cell retention in venous thrombi

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

Ranking reactive glutamines in the fibrinogen αC region that are targeted by blood coagulant factor XIII

Contact Info

Product

Resources

About