# Mechanisms of mechano-chemical rupture of blood clots and thrombi

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $639,595

## Abstract

Mechanisms of mechano-chemical rupture of blood clots and thrombi
Prashant K. Purohit, John L. Bassani, Valeri Barsegov and John W. Weisel
The goal of this proposal is to explore and understand the fracture toughness of blood clots and thrombi, thus
providing a mechanistic basis for life-threatening thrombotic embolization. A combination of experiments,
theoretical modeling and computer simulations will reveal how mechanical stresses (due to blood flow) in
synergy with enzymatic lysis induce structural damage from the molecular to continuum scales and affect the
propensity of a clot to embolize. The specific aims of this proposal are: (1) Measure and model fracture
toughness of fibrin gels in quasi-static conditions, (2) Investigate rate dependent dissipative effects on
toughness of fibrin gels, and (3) Study the effects of blood cells, prothrombotic blood composition,
and fibrinolysis on rupture of blood clots. In Specific Aim (SA) 1, we will measure toughness of fibrin clots
and provide a structural basis for rupture at the micron and nanometer scales. In SA2, we will delve into the
thermodynamics and rate-dependence of the fracture of fibrin gels, including fluid flow through pores and fluid
drag on fibrin fibers to capture how energy dissipation increases toughness. In the translational SA3, we will
investigate toughness of physiologically relevant clots with effects of platelets, red blood cells, and neutrophils
in the absence and presence of the physiological fibrinolytic activator (tPA). We will also study the rupture of
clots made from the blood of venous thromboembolism patients to explore the effects of (pro)thrombotic
alterations of blood composition on clot mechanical stability. Our preliminary studies show that i) the toughness
of cross-linked fibrin gels is in the range of those for synthetic hydrogels, ii) the addition of tPA to a crack tip
reduces the loads for crack growth, iii) fibers are aligned and broken along the tensile direction at the crack tip,
and iv) crack propagation results from the rupture of covalent and non-covalent bonds. We also developed v)
dynamic force spectroscopy in silico to mechanically test fibrin fibers and fibrin networks using pulling
simulations and vi) atomic stress approach to map the stress-strain fields using the output from simulations.
We will use continuum and finite element models of swellable biopolymer hydrogels, and statistical mechanical
models for the forced unfolding of fibrin molecules. We will employ multiscale computational modeling based
on Molecular Dynamics simulations of atomic structures of fibrin fibers, and Langevin simulations of fibrin
networks accelerated on Graphics Processing Units. The proposed experiments cover the whole gamut of
macroscopic tensile tests, shear rheometry, electron microscopy and confocal microscopy to visualize and
quantitate the structural alterations of ruptured blood clots. Our experiments and modeling will help us to
understand the mechanisms of th...

## Key facts

- **NIH application ID:** 10165811
- **Project number:** 5R01HL148227-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Prashant Kishore Purohit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $639,595
- **Award type:** 5
- **Project period:** 2020-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165811

## Citation

> US National Institutes of Health, RePORTER application 10165811, Mechanisms of mechano-chemical rupture of blood clots and thrombi (5R01HL148227-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165811. Licensed CC0.

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