OC 59.5 - Rupture Mechanics of Blood Clots: Influence of Fibrin Structure on the Rupture Resistance

Tuesday, June 25, 2024

10:30 – 10:45 ICT

Room: 208 A-D

Presenting Author(s)

Ranjini Ramanujam

Doctoral student
Rutgers University
New Brunswick, New Jersey, United States

Co-Author(s)

FM

Farkhad Maksudov

Doctoral student
University of Massachusetts Lowell
Lowell, Massachusetts, United States
Rebecca A. Risman

Doctoral student
Rutgers University
Piscataway, New Jersey, United States
Rustem I. Litvinov

Senior Research Investigator
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Philadelphia, Pennsylvania, United States
John W. Weisel

Professor of Cell and Developmental Biology
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Philadelphia, Pennsylvania, United States
Jb

John bassani

Professor
university of Pennsylvania
Philadelphia, Pennsylvania, United States
VB

Valeri Barsegov

Associate Professor
University of Massachusetts Lowell
Lowell, Massachusetts, United States
PK

Prashant K. Purohit

Associate Professor
university of Pennsylvania
Philadelphia, Pennsylvania, United States
VT

Valerie Tutwiler

Assistant Professor
Rutgers University
New Brunswick, New Jersey, United States

Background: Thrombotic embolization is a leading cause of mortality, yet we know little about clot rupture mechanics. Fibrin provides the main structural and mechanical stability to blood clots. Previous studies have shown that altering the concentration of coagulation activators (thrombin or tissue factor (TF)) has a significant impact on fibrin structure and viscoelastic properties, but rupture properties are mostly unknown. Toughness, which corresponds to the ability to resist rupture, is independent of viscoelastic properties.

Aims: In this study, we aimed to assess the role of fibrin structure modulated with different TF concentrations on the rupture resistance of blood clots.

Methods: We used varying TF concentrations to alter the structure and toughness of human plasma clots. We performed single-edge notch rupture tests to examine fibrin toughness under a constant strain rate (Fig.1A) and we assessed viscoelastic mechanics using rheology. We utilized fluorescent confocal and scanning electron microscopy (SEM) (Fig.1B) to quantify the fibrin network structure under varying TF concentrations.

Results: Our results revealed that increased TF concentration resulted in increased fibrin density (Fig.1C) with a corresponding reduction in network pore size, thinner (Fig.1D) and shorter (not shown) fibrin fibers. Increasing TF concentration yielded a maximum toughness at mid-TF concentration (Fig.1E), while the low TF concentration samples showed the highest stiffness (not shown). We show that fibrin diameter and network density underlie a complex role in influencing the rupture resistance of blood clots, resulting in a non-monotonic relationship between TF and toughness, and revealing that fibrin structural changes significantly impact rupture resistance.

Conclusion(s): Variations in fibrin density, fiber diameter, and fiber length give rise to a complex influence of fibrin structure on rupture. The differences in mechanical responses point to the importance of studying the structure-function relationships of fibrin networks formed under different conditions, which may be predictive of the tendency for embolization.