Format

Send to

Choose Destination
Biophys J. 2018 Feb 27;114(4):978-991. doi: 10.1016/j.bpj.2017.12.034.

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

Author information

1
Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland.
2
Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania.
3
Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland. Electronic address: jaques.reifman.civ@mail.mil.

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 size and its viscous resistance. Finally, TF effects on blood flow occlusion were more pronounced for the longer thrombogenic surface than for the shorter one. Our results suggest that TF surface density and its exposure area can independently enhance both the clot's occlusivity and its resistance to blood flow. These findings provide, to our knowledge, new insights into how TF affects thrombus growth in time and space under flow.

PMID:
29490257
PMCID:
PMC5984989
[Available on 2019-02-27]
DOI:
10.1016/j.bpj.2017.12.034
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center