Multiscale Network Modeling of Fibrin Fibers and Fibrin Clots with Protofibril Binding Mechanics.

Sumith Yesudasan,Rodney D Averett

doi:10.3390/polym12061223

Abstract

The multiscale mechanical behavior of individual fibrin fibers and fibrin clots was modeled by coupling atomistic simulation data and microscopic experimental data. We propose a new protofibril element composed of a nonlinear spring network, and constructed this based on molecular simulations and atomic force microscopy results to simulate the force extension behavior of fibrin fibers. This new network model also accounts for the complex interaction of protofibrils with one another, the effects of the presence of a solvent, Coulombic attraction, and other binding forces. The network model was formulated to simulate the force–extension mechanical behavior of single fibrin fibers from atomic force microscopy experiments, and shows good agreement. The validated fibrin fiber network model was then combined with a modified version of the Arruda–Boyce eight-chain model to estimate the force extension behavior of the fibrin clot at the continuum level, which shows very good correlation. The results show that our network model is able to predict the behavior of fibrin fibers as well as fibrin clots at small strains, large strains, and close to the break strain. We used the network model to explain why the mechanical response of fibrin clots and fibrin fibers deviates from worm-like chain behavior, and instead behaves like a nonlinear spring.

Highlights

Constitutive modeling of fibrin fibers and fibrin clots is still a challenging topic and is necessary for understanding the origin of the mechanical properties under various loading conditions.Despite advancements in experimental methods to determine the molecular composition and crystal structure of fibrinogen, a major constituent of blood clots, our understanding of fibrin clot mechanics remains poorly understood, and is crucial in developing thrombolytic therapies and diagnosis of thrombosis [1]
The goal of this work was to construct the biopolymer complex into a nonlinear entities, whose properties were estimated from atomic force microscopy (AFM) measurements or from network of mechanical entities, whose properties were estimated from atomic force microscopy molecular dynamics (MD) simulations
A multiscale network model for fibrin fibers (Model 2) and fibrin clots (Model 3) was developed that is suitable for incorporation into standard continuum level models

Summary

Introduction

Constitutive modeling of fibrin fibers and fibrin clots is still a challenging topic and is necessary for understanding the origin of the mechanical properties under various loading conditions.Despite advancements in experimental methods to determine the molecular composition and crystal structure of fibrinogen, a major constituent of blood clots, our understanding of fibrin clot mechanics remains poorly understood, and is crucial in developing thrombolytic therapies and diagnosis of thrombosis [1]. Researchers have utilized both the three-chain model and eight-chain model to determine the constitutive response of fibrin clots [2]. These models provide benefits for modeling small-strain behavior, the results from these studies show inadequacies at fully representing the constitutive behavior of fibrin clots at higher strains [2]. Fibrin clot polymerization modeling [3,4] and fibrin mechanics [2,5,6] are important research topics for the scientific community. Among these methods, the eight-chain model of fibrin fibers [2]

Objectives

Methods

Conclusion