OC 09.2 - Biomechanics, Energetics, and Structural Basis of Rupture of Fibrin Networks with Varying Density

Saturday, June 24, 2023

13:15 – 13:30 ET

Room: 519

Session Available As: On-Demand

Presenting Author(s)

Ranjini Ramanujam, MS

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
CN

Chandrasekaran Nagaswami

Senior researcher
university of Pennsylvania
Philadelphia, Massachusetts, United States
Rustem I. Litvinov, MD, PhD

Senior researcher
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pennsylvania, United States
John W. Weisel, PhD

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

Valeri Barsegov

Associate Professor
University of Massachusetts Lowell
Lowell, Massachusetts, United States
Valerie Tutwiler, PhD

Assistant Professor
Rutgers-State University of New Jersey
Piscataway, New Jersey, United States

Background: Fibrin is a self-assembling, viscoelastic polymeric biomaterial that provides mechanical and structural stability to blood clots (thrombi). A life-threatening complication of thrombosis is embolization, which occurs when a portion of the thrombus ruptures and becomes lodged in the blood vessels downstream. Embolization of venous thrombi increases the mortality risk by 30%.

Aims: To investigate the influence of fibrin(ogen) concentration on the microstructural and mechanical resistance of clots to rupture.

Methods: Single-edge notch fracture tests were performed to examine fibrin rupture under a constant strain rate (Fig.1A) to determine the mechanical properties of rupture. Confocal and scanning electron microscopy were used to quantify the fibrin network structure. A theoretical fluctuating spring (FS) model was used to characterize the relationship between fibrin(ogen) concentration and rupture resistance of fibrin clots.

Results: Our results revealed that increasing fibrin(ogen) concentrations from 1 to 5 g/l resulted in an increase in rupture resistance from 127 to 365 J/m3. The network structure became denser [0.98 to 12.2 fiber pixels/total voxel (%), p< 0.0001] with thicker fibers (0.14 to 0.3 µm, p< 0.0001) with increasing fibrin(ogen) concentrations. At low (1 g/l) and normal (2.7 g/l) fibrinogen concentrations, fibrin fibers straightened first (regime I) and then stretched (regime II), as shown by the constant slope of the stress-strain curve. In contrast, at higher fibrinogen concentration (5 g/l), the fiber straightening and stretching occurred simultaneously as shown by an increase in slope of the stress-strain curve (Fig.1B). The results obtained demonstrate that changes in fibrin structure due to varying fibrin(ogen) concentration drastically alter clot mechanical stability

Conclusion(s): These results indicate a substantial role for fibrin clot density in the tendency for embolization and the resistance of fibrin clots to rupture.

Learning Objectives:

Learn about the importance of studying the mechanical properties of fibrin
Learn the relationship between fibrin microstructure and rupture resistance of blood clots
Understand the influence of fibrinogen concentration on the rupture resistance of blood clots