Impact of Tissue Factor Localization on Blood Clot Structure and Resistance under Venous Shear

Biophysical Journal
Vijay GovindarajanAlexander Y Mitrophanov

Abstract

The structure and growth of a blood clot depend on the localization of tissue factor (TF), which can trigger clotting during the hemostatic process or promote thrombosis when exposed to blood under pathological conditions. We sought to understand how the growth, structure, and mechanical properties of clots under flow are shaped by the simultaneously varying TF surface density and its exposure area. We used an eight-channel microfluidic device equipped with a 20- or 100-μm-long collagen surface patterned with lipidated TF of surface densities ∼0.1 and ∼2 molecules/μm2. Human whole blood was perfused at venous shear, and clot growth was continually measured. Using our recently developed computational model of clot formation, we performed simulations to gain insights into the clot's structure and its resistance to blood flow. An increase in TF exposure area resulted not only in accelerated bulk platelet, thrombin, and fibrin accumulation, but also in increased height of the platelet mass and increased clot resistance to flow. Moreover, increasing the TF surface density or exposure area enhanced platelet deposition by approximately twofold, and thrombin and fibrin generation by greater than threefold, thereby increasing both clot ...Continue Reading

References

Jan 30, 1992·The New England Journal of Medicine·V FusterJ H Chesebro
Jul 1, 1991·Biophysical Journal·E C Eckstein, F Belgacem
Jul 27, 1989·Biochimica Et Biophysica Acta·B BlombäckN Aslund
Dec 31, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·Y P WuJ J Sixma
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·S F YanD Stern
Mar 24, 2000·Atherosclerosis·A G ZamanJ J Badimon
Sep 5, 2003·Pathophysiology of Haemostasis and Thrombosis·Bruce Furie, Barbara C Furie
May 1, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Nigel Mackman
Nov 25, 2004·Hematology·José A LópezAgnes Y Y Lee
Aug 5, 2005·Annals of Biomedical Engineering·Paul D GoodmanKenneth A Solen
Oct 29, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Dougald M Monroe, Maureane Hoffman
Feb 10, 2006·Blood Cells, Molecules & Diseases·Nigel Mackman
Jan 9, 2007·Blood Reviews·Alisa S Wolberg
Jun 9, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Nigel MackmanNigel S Key
Jun 26, 2007·Biophysical Journal·Christian J KastrupRustem F Ismagilov
Aug 1, 2007·Journal of Thrombosis and Haemostasis : JTH·B Furie, B C Furie
Feb 22, 2008·Nature·Nigel Mackman
Aug 16, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Feng ShenRustem F Ismagilov
May 26, 2009·Nature Medicine·Warwick S NesbittShaun P Jackson
Jul 14, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Saulius ButenasKenneth G Mann
May 5, 2010·Mathematical Medicine and Biology : a Journal of the IMA·Karin Leiderman, Aaron L Fogelson
Jan 1, 2005·Annual Review of Fluid Mechanics·Aleksander S Popel, Paul C Johnson
Jan 13, 2011·Thrombosis and Haemostasis·Alexander G G Turpie, Charles Esmon
Aug 13, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Anetta Undas, Robert A S Ariëns
Apr 21, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Thomas V ColaceScott L Diamond
Sep 18, 2012·Journal of Thrombosis and Haemostasis : JTH·J D WelshS L Diamond
Oct 26, 2012·Bulletin of Mathematical Biology·Karin Leiderman, Aaron L Fogelson
Jul 23, 2013·Biophysical Journal·David L Bark, David N Ku
Dec 19, 2013·Journal of Thrombosis and Haemostasis : JTH·A A Onasoga-JarvisK B Neeves

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Citations

May 6, 2019·Biomechanics and Modeling in Mechanobiology·Alexander Y MitrophanovJaques Reifman
May 23, 2019·International Journal for Numerical Methods in Biomedical Engineering·Nicholas A Danes, Karin Leiderman
Jul 10, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Alexander Y MitrophanovJaques Reifman
Sep 12, 2020·Hämostaseologie·Dmitry Y NechipurenkoMikhail A Panteleev
Feb 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Heta Jigar PanchalLeanne F Harris
Jan 23, 2020·Biomicrofluidics·Sarah E MenaMark A Burns
Dec 26, 2018·Clinical Hemorheology and Microcirculation·Hoyoon LeeSehyun Shin

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Methods Mentioned

BETA
blood collection
rheology

Software Mentioned

custom
FLUENT
MATLAB
ImageJ

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