[Paper Review] Multiscale Network Model for Fibrin Fibers and Fibrin Clot with Protofibril Binding Mechanics

Sumith Yesudasan, Rodney D. Averett|arXiv (Cornell University)|Aug 13, 2018

Blood properties and coagulation22 references3 citations

TL;DR

This paper proposes a multiscale network model that integrates atomistic simulations and experimental data to simulate the nonlinear mechanical behavior of fibrin fibers and clots. By modeling protofibrils as nonlinear spring networks with binding forces, the model accurately predicts force-extension curves of single fibers and continuum-level clots, explaining their deviation from worm-like chain behavior and validating its predictive power across small to large strains, including near failure.

ABSTRACT

The multiscale behavior of the individual fibrin fibers and fibrin clots is modeled by coupling atomistic simulation data and microscopic experimental data. We propose a protofibril element made up of nonlinear spring network, constructed based on the molecular simulation 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 each other, effect of presence of solvent, Coulombic attraction and other binding forces. The network model is applied to simulate the force extension behavior of single fibrin fiber from atomic force microscopy experiments and shows good agreement. Thus validated fibrin fiber network model is then combined with a modified version of Arruda-Boyce eight chain model to estimate the force extension behavior of continuum level fibrin clot, which shows very good correlation. The results show that this network model is able to predict the behavior of fibrin fibers as well as fibrin clot at small strains, large strains and even closer to the break strain. We use the network model to explain why the fibrin clots and fibers doesn't behave like a worm like chain, instead behaves like a nonlinear spring.

Motivation & Objective

• To develop a predictive multiscale model that captures the mechanical behavior of fibrin fibers and clots across multiple length and time scales.
• To explain why fibrin fibers and clots do not follow worm-like chain behavior but instead exhibit nonlinear spring-like mechanics.
• To integrate atomistic simulation data and atomic force microscopy (AFM) experiments into a unified mechanical network model.
• To account for complex interactions such as protofibril binding, solvent effects, and Coulombic forces in the mechanical response.
• To validate the model against experimental AFM data and extend its application to continuum-level clot mechanics using a modified Arruda-Boyce model.

Proposed method

• Construct a protofibril element as a nonlinear spring network based on molecular dynamics simulation data and AFM measurements.
• Incorporate binding forces including Coulombic attraction and solvent effects into the protofibril network model.
• Use the validated protofibril network to simulate the force-extension behavior of single fibrin fibers and compare with AFM experiments.
• Combine the protofibril network model with a modified Arruda-Boyce eight-chain model to simulate continuum-level fibrin clot mechanics.
• Calibrate the model parameters using experimental data to ensure agreement across small, large, and near-failure strains.
• Validate the model’s predictive capability by comparing simulated force-extension curves with experimental observations.

Experimental results

Research questions

• RQ1 How do protofibril interactions and binding mechanics contribute to the nonlinear elasticity of fibrin fibers?
• RQ2 Why does fibrin fiber behavior deviate from the worm-like chain model under mechanical loading?
• RQ3 Can a multiscale network model accurately predict the force-extension response of single fibrin fibers across physiological strain ranges?
• RQ4 How can the mechanical properties of individual fibrin fibers be upscaled to predict the behavior of a fibrin clot at the continuum level?
• RQ5 What role do solvent effects and electrostatic forces play in the mechanical response of fibrin networks?

Key findings

• The protofibril network model successfully reproduces the force-extension behavior of single fibrin fibers as measured by atomic force microscopy.
• The model demonstrates that fibrin fibers exhibit nonlinear spring-like mechanics rather than worm-like chain behavior due to inter-protofibril binding and structural reorganization.
• The inclusion of Coulombic attraction and solvent effects significantly improves the model’s accuracy in capturing mechanical responses.
• The hybrid model, combining the protofibril network with a modified Arruda-Boyce eight-chain model, shows strong correlation with experimental data for fibrin clots at the continuum scale.
• The model accurately predicts mechanical behavior across small strains, large strains, and near the break strain, indicating robustness over a wide deformation range.
• The validated model provides a mechanistic explanation for the mechanical resilience of fibrin clots through protofibril network reorganization and binding forces.