MODELING FIBRIN POLYMERIZATION IN BLOOD FLOW WITH DISCRETE-PARTICLES (original) (raw)
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A discrete-particle model of blood dynamics in capillary vessels
Journal of Colloid and Interface Science, 2003
We investigate the physical mechanism of aggregation of red blood cells (RBC) in capillary vessels, using a discrete particle model. This model can accurately capture the scales from 0.001µm to 100µm, far below the scales, which can be modeled numerically with classical computational fluid dynamics. We use a discrete-particle model in 3D for modeling the flow of plasma and RBCs in a capillary tube. The two situations involving necking and no necking have been considered. The flexible viscoelastic red blood cells and the walls of the elastic vessel are made up of solid particles held together by elastic harmonic forces. The blood plasma is represented by a system of dissipative fluid particles. We have simulated the flow of cells of different shapes, such as normal and "sickle" cells. The cells coagulate in spite of the absence of adhesive forces in the model. The total number of fluid and solid particles used ranges from 1 to 3 million. We conclude that aggregation of red blood cells in capillary vessels is stimulated by depletion forces and hydrodynamic interactions. The cluster of "sickle" cells formed in the necking of the conduit efficiently decelerates the flow, while normal cells can pass through. These qualitative results from numerical simulations accord well with laboratory findings.
Fibrin polymerization simulation using a reactive dissipative particle dynamics method
Biomechanics and Modeling in Mechanobiology
The study on the polymerization of fibrinogen molecules into fibrin monomers and eventually a stable, mechanically robust fibrin clot is a persistent and enduring topic in the field of thrombosis and hemostasis. Despite many research advances in fibrin polymerization, the change in the structure of fibrin clots and its influence on the formation of a fibrous protein network are still poorly understood. In this paper, we develop a new computational method to simulate fibrin clot polymerization using dissipative particle dynamics simulations. With an effective combination of reactive molecular dynamics formularies and many body dissipative particle dynamics principles, we constructed the reactive dissipative particle dynamics (RDPD) model to predict the complex network formation of fibrin clots and branching of the fibrin network. The 340 kDa fibrinogen molecule is converted into a spring-bead coarse-grain system with 11 beads using a topology representing network algorithm, and using RDPD, we simulated polymerization and formation of the fibrin clot. The final polymerized structure of the fibrin clot qualitatively agrees with experimental results from the literature, and to the best of our knowledge this is the first molecular-based study that simulates polymerization and structure of fibrin clots.
Modelling thrombosis using dissipative particle dynamics method
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 2008
Aim . Arterial occlusion is a leading cause of cardiovascular disease. The main mechanism causing vessel occlusion is thrombus formation, which may be initiated by the activation of platelets. The focus of this study is on the mechanical aspects of platelet-mediated thrombosis which includes the motion, collision, adhesion and aggregation of activated platelets in the blood. A review of the existing continuum-based models is given. A mechanical model of platelet accumulation onto the vessel wall is developed using the dissipative particle dynamics (DPD) method in which the blood (i.e. colloidal-composed medium) is treated as a group of mesoscale particles interacting through conservative, dissipative, attractive and random forces. Methods . Colloidal fluid components (plasma and platelets) are discretized by mesoscopic (micrometre-size) particles that move according to Newton's law. The size of each mesoscopic particle is small enough to allow tracking of each constituent of the...
Mathematical model of fibrin polymerization
Blood clotting system (BCS) modelling is an important issue with a plenty of applications in medicine and biophysics. The BCS main function is to form a localized clot at the site of injury preventing blood loss. Mutual influence of fibrin clot consisting mainly of fibrin polymer gel and blood flow is an important factor for BCS to function properly. The process of fibrin polymer mesh formation has not adequately been described by current mathematical models. That is why it is not possible to define the borders of growing clot and model its interaction with a blood flow. This paper main goal is to propose physically well-founded mathematical model of fibrin polymerization and gelation. The proposed model defines the total length of fibrin polymer fibers in the unit volume, determines a position of the border between gel and liquid and allows to evaluate the permeability of growing gel. Without significant structural changes the proposed model could be modified to include the blood shear rate influence on the fibrin polymerization and gelation.
Modelling fibrinolysis: a 3D stochastic multiscale model
Mathematical Medicine and Biology, 2012
Fibrinolysis, the proteolytic degradation of the fibrin fibres that stabilize blood clots, is initiated when tissue-type plasminogen activator (tPA) activates plasminogen to plasmin, the main fibrinolytic enzyme. Many experiments have shown that coarse clots made of thick fibres lyse more quickly than fine clots made of thin fibres, despite the fact that individual thick fibres lyse more slowly than individual thin fibres. The generally accepted explanation for this is that a coarse clot with fewer fibres to transect will be degraded faster than a fine clot with a higher fibre density. Other experiments show the opposite result. The standard mathematical tool for investigating fibrinolysis has been deterministic reaction-diffusion models, but due to low tPA concentrations, stochastic models may be more appropriate. We develop a 3D stochastic multiscale model of fibrinolysis. A microscale model representing a fibre cross section and containing detailed biochemical reactions provides information about single fibre lysis times, the number of plasmin molecules that can be activated by a single tPA molecule and the length of time tPA stays bound to a given fibre cross section. Data from the microscale model are used in a macroscale model of the full fibrin clot, from which we obtain lysis front velocities and tPA distributions. We find that the fibre number impacts lysis speed, but so does the number of tPA molecules relative to the surface area of the clot exposed to those molecules. Depending on the values of these two quantities (tPA number and surface area), for given kinetic parameters, the model predicts coarse clots lyse faster or slower than fine clots, thus providing a possible explanation for the divergent experimental observations.
Modelling fibrinolysis: 1D continuum models
Mathematical Medicine and Biology, 2012
Fibrinolysis is the enzymatic degradation of the fibrin mesh that stabilizes blood clots. Experiments have shown that coarse clots made of thick fibres sometimes lyse more quickly than fine clots made of thin fibres, despite the fact that individual thick fibres lyse more slowly than individual thin fibres. This paper aims at using a 1D continuum reaction-diffusion model of fibrinolysis to elucidate the mechanism by which coarse clots lyse more quickly than fine clots. Reaction-diffusion models have been the standard tool for investigating fibrinolysis, and have been successful in capturing the wave-like behaviour of lysis seen in experiments. These previous models treat the distribution of fibrin within a clot as homogeneous, and therefore cannot be used directly to study the lysis of fine and coarse clots. In our model, we include a spatially heterogeneous fibrin concentration, as well as a more accurate description of the role of fibrin as a cofactor in the activation of the lytic enzyme. Our model predicts spatio-temporal protein distributions in reasonable quantitative agreement with experimental data. The model also predicts observed behaviour such as a front of lysis moving through the clot with an accumulation of lytic proteins at the front. In spite of the model improvements, however, we find that 1D continuum models are unable to accurately describe the observed differences in lysis behaviour between fine and coarse clots. Features of the problems that lead to the inaccuracy of 1D continuum models are discussed. We conclude that higher-dimensional, multiscale models are required to investigate the effect of clot structure on lysis behaviour.
Journal of Molecular Modeling, 2018
Studies suggest that patients with deep vein thrombosis and diabetes often have hypercoagulable blood plasma, leading to a higher risk of thromboembolism formation through the rupture of blood clots, which may lead to stroke and death. Despite many advances in the field of blood clot formation and thrombosis, the influence of mechanical properties of fibrin in the formation of thromboembolisms in platelet-poor plasma is poorly understood. In this paper, we combine the concepts of reactive molecular dynamics and coarse-grained molecular modeling to predict the complex network formation of fibrin clots and the branching of fibrin monomers. The 340-kDa fibrinogen molecule was converted into a coarse-grained molecule with nine beads, and using our customized reactive potentials, we simulated the formation and polymerization process of a fibrin clot. The results show that higher concentrations of thrombin result in higher branch-point formation in the fibrin clot structure. Our results a...
Multiscale Mechanics of Fibrin Polymer
Bulletin of the American …, 2009
Blood clots and thrombi consist primarily of fibrin, a branched, open mesh of polymeric fibers made of protein monomers, with a remarkable and unexplained extensibility and elasticity. Understanding the origin of fibrin mechanics may ultimately be significant for modulating ...