# Experiment-based multi-scale modeling of the tensile and compressive deformations of fibrin

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $387,249

## Abstract

Experiment-based multi-scale modeling of the tensile and compressive deformations of fibrin
 Prashant K. Purohit and John W. Weisel
University of Pennsylvania, Philadelphia, PA 19104.
Abstract: The research objective of this proposal is to measure, model and predict the tensile and
compressive response of fibrin clots at the molecular and continuum scales. This is important because there
are no comprehensive models that link the molecular mechanics to the macroscopic deformation of clots and
thrombi, even though they experience deformation/alteration at all scales during their normal function in
hemostasis and in pathological situations of thrombosis. We have shown that macroscale fibrin clots can be
stretched to three or four times their original length in uniaxial tension due to mechanical unfolding of fibrin
monomers at the nanometer scale. In compression, we have shown that the deformation of a clot is analogous
to that of a foam and proceeds by the motion of a compression front, behind which the network densifies due
to buckling of fibers and creation of inter-fiber contacts. These features are captured in our models that can
quantitatively describe and predict how molecular and fiber level mechanics has implications for the
macroscopic response of clots. Our models allow us to tune the macroscale mechanical behavior of clots by
altering the molecular building blocks and the structural parameters of the network. This idea will be put to the
test when we (a) modulate the equilibrium tensile response of clots by altering the network structural
parameters, and (b) investigate how cross-linking of oligomers affects the dependence of the tensile response
on the strain rate. We can also alter the nanoscale structure of fibrin and use our model to predict the
consequences for macroscopic clots. Our target is the  C region of fibrin, which is known to vary depending
on the species and has been shown to play a part in controlling the tensile stiffness and extensibility of single
fibrin fibers as well fibrin clots. For compression, we will show that the deformation of platelet-poor plasma
clots, platelet-rich plasma clots, whole blood clots and thrombi is also foam-like, and then predict and measure
their response to localized loads. Such localized loads could be encountered in clinical situations, such as the
interaction of catheters or bubbles with thrombi. We will also investigate the effect of the  C region on the
compression response of clots. Our models are based on continuum mechanical principles for the study of
polymeric materials and foams, as well as statistical mechanics models describing forced unfolding of single
protein molecules. The proposed experiments cover the whole gamut of macroscopic uniaxial tension tests,
atomic force microscopy experiments including stretching of oligomers and indentation of clots, rheometry to
measure the storage and loss moduli in compression, electron microscopy as well as fluorescence microscopy
to visu...

## Key facts

- **NIH application ID:** 9960572
- **Project number:** 5R01HL135254-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Prashant Kishore Purohit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,249
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960572

## Citation

> US National Institutes of Health, RePORTER application 9960572, Experiment-based multi-scale modeling of the tensile and compressive deformations of fibrin (5R01HL135254-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960572. Licensed CC0.

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