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Rupture of blood clots: Mechanics and pathophysiology

Fibrin is the three-dimensional mechanical scaffold of protective blood clots that stop bleeding and pathological thrombi that obstruct blood vessels. Fibrin must be mechanically tough to withstand rupture, after which life-threatening pieces (thrombotic emboli) are carried downstream by blood flow....

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Autores principales: Tutwiler, Valerie, Singh, Jaspreet, Litvinov, Rustem I., Bassani, John L., Purohit, Prashant K., Weisel, John W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449685/
https://www.ncbi.nlm.nih.gov/pubmed/32923647
http://dx.doi.org/10.1126/sciadv.abc0496
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author Tutwiler, Valerie
Singh, Jaspreet
Litvinov, Rustem I.
Bassani, John L.
Purohit, Prashant K.
Weisel, John W.
author_facet Tutwiler, Valerie
Singh, Jaspreet
Litvinov, Rustem I.
Bassani, John L.
Purohit, Prashant K.
Weisel, John W.
author_sort Tutwiler, Valerie
collection PubMed
description Fibrin is the three-dimensional mechanical scaffold of protective blood clots that stop bleeding and pathological thrombi that obstruct blood vessels. Fibrin must be mechanically tough to withstand rupture, after which life-threatening pieces (thrombotic emboli) are carried downstream by blood flow. Despite multiple studies on fibrin viscoelasticity, mechanisms of fibrin rupture remain unknown. Here, we examined mechanically and structurally the strain-driven rupture of human blood plasma–derived fibrin clots where clotting was triggered with tissue factor. Toughness, i.e., resistance to rupture, quantified by the critical energy release rate (a measure of the propensity for clot embolization) of physiologically relevant fibrin gels was determined to be 7.6 ± 0.45 J/m(2). Finite element (FE) simulations using fibrin material models that account for forced protein unfolding independently supported this measured toughness and showed that breaking of fibers ahead the crack at a critical stretch is the mechanism of rupture of blood clots, including thrombotic embolization.
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spelling pubmed-74496852020-09-11 Rupture of blood clots: Mechanics and pathophysiology Tutwiler, Valerie Singh, Jaspreet Litvinov, Rustem I. Bassani, John L. Purohit, Prashant K. Weisel, John W. Sci Adv Research Articles Fibrin is the three-dimensional mechanical scaffold of protective blood clots that stop bleeding and pathological thrombi that obstruct blood vessels. Fibrin must be mechanically tough to withstand rupture, after which life-threatening pieces (thrombotic emboli) are carried downstream by blood flow. Despite multiple studies on fibrin viscoelasticity, mechanisms of fibrin rupture remain unknown. Here, we examined mechanically and structurally the strain-driven rupture of human blood plasma–derived fibrin clots where clotting was triggered with tissue factor. Toughness, i.e., resistance to rupture, quantified by the critical energy release rate (a measure of the propensity for clot embolization) of physiologically relevant fibrin gels was determined to be 7.6 ± 0.45 J/m(2). Finite element (FE) simulations using fibrin material models that account for forced protein unfolding independently supported this measured toughness and showed that breaking of fibers ahead the crack at a critical stretch is the mechanism of rupture of blood clots, including thrombotic embolization. American Association for the Advancement of Science 2020-08-26 /pmc/articles/PMC7449685/ /pubmed/32923647 http://dx.doi.org/10.1126/sciadv.abc0496 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Tutwiler, Valerie
Singh, Jaspreet
Litvinov, Rustem I.
Bassani, John L.
Purohit, Prashant K.
Weisel, John W.
Rupture of blood clots: Mechanics and pathophysiology
title Rupture of blood clots: Mechanics and pathophysiology
title_full Rupture of blood clots: Mechanics and pathophysiology
title_fullStr Rupture of blood clots: Mechanics and pathophysiology
title_full_unstemmed Rupture of blood clots: Mechanics and pathophysiology
title_short Rupture of blood clots: Mechanics and pathophysiology
title_sort rupture of blood clots: mechanics and pathophysiology
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449685/
https://www.ncbi.nlm.nih.gov/pubmed/32923647
http://dx.doi.org/10.1126/sciadv.abc0496
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