Modelling thrombosis using dissipative particle dynamics method (original) (raw)
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Modelling of thrombus growth and growth stop in flow by the method of dissipative particle dynamics
Russian Journal of Numerical Analysis and Mathematical Modelling, 2012
Platelet aggregation at the site of vascular injury leads to formation of a hemostatic plug covering the injury site, or a thrombus in the pathological case. The mechanisms that control clot growth and which lead to growth arrest are not yet completely understood. In order to study these mechanisms theoretically, we use the Dissipative Particle Dynamics method which allows us to model individual platelets in the flow and in the clot. The model takes into account different stages of platelet adhesion process. First, a platelet is captured reversibly by the aggregate, and then it activates and adheres firmly becoming a part of its core. We suggest that the core of the clot is composed of platelets unable to attach new platelets from the flow due to activation by thrombin and/or wrapping by the fibrin mesh. The simulations are in a good agreement with the experimental results . Modelling shows that stopping of growth of a hemostatic plug (and thrombus) can result from removing its exterior part by flow and exposing its non-adhesive core to the flow.
Cellular and molecular bioengineering, 2014
We developed a multiscale particle-based model of platelets, to study the transport dynamics of shear stresses between the surrounding fluid and the platelet membrane. This model facilitates a more accurate prediction of the activation potential of platelets by viscous shear stresses - one of the major mechanisms leading to thrombus formation in cardiovascular diseases and in prosthetic cardiovascular devices. The interface of the model couples coarse-grained molecular dynamics (CGMD) with dissipative particle dynamics (DPD). The CGMD handles individual platelets while the DPD models the macroscopic transport of blood plasma in vessels. A hybrid force field is formulated for establishing a functional interface between the platelet membrane and the surrounding fluid, in which the microstructural changes of platelets may respond to the extracellular viscous shear stresses transferred to them. The interaction between the two systems preserves dynamic properties of the flowing platelets...
Microvascular Research, 2008
When the size of individual blood constituents [e.g., red blood cells (RBCs), white blood cells, platelets] becomes comparable to the size of blood vessels, the interactions among blood constituents in determining the blood behavior can no longer be ignored. In this paper, we have developed a comprehensive computational model to simulate the motion of an individual platelet in the plasma medium and its binding to the microvessel wall. The model is based on a Discrete Particle Dynamics (DPD) algorithm, in which blood plasma, platelets and the vessel walls are treated as a group of discretized mesoscopic size particles interacting through conservative, dissipative and random forces. Deposition (i.e., binding) of platelets is modeled by considering attractive forces at the vessel wall, which is characterized by the values of the effective spring constant for platelet adhesion. To test this model, we simulated platelet deposition in a perfusion chamber. By matching the simulation results to experimental data, the effective platelet spring constants were determined and were found to be approximately 50 N/m, which is within a physiologically relevant range. It is demonstrated that the DPD analysis offers the capability of simulating the time-dependent binding of platelets. We conclude that this model provides a new approach for studying the interaction among blood constituents.
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.
Modelling of thrombus growth in flow with a DPD-PDE method
Journal of Theoretical Biology, 2013
Hemostatic plug covering the injury site (or a thrombus in the pathological case) is formed due to the complex interaction of aggregating platelets with biochemical reactions in plasma that participate in blood coagulation. The mechanisms that control clot growth and which lead to growth arrest are not yet completely understood. We model them with numerical simulations based on a hybrid DPD-PDE model. Dissipative particle dynamics (DPD) is used to model plasma flow with platelets while fibrin concentration is described by a simplified reaction-diffusion-advection equation.
MODELING FIBRIN POLYMERIZATION IN BLOOD FLOW WITH DISCRETE-PARTICLES
2004
Excessive clotting can cause bleeding over a vast capillary areas contributing to stroke, heart attack or blindness. We study the mesoscopic dynamics of clotting by using a discrete-particle model. We assume that the plasma consists of fluid particles containing fibrin monomers, while the red blood cells and capillary walls are modeled using elastic mesh of "solid" particles. The fluid particles interact with each other with a short -ranged, repulsive dissipative force. The particles containing fibrin monomers have a dual character. The polymerization of fibrin monomers into hydrated fibrins is modeled by the change of the interactions between fluid particles from repulsive to attractive forces. This process occurs with a probability being an increasing function of a local density. We study the blood flow in microscopic capillary vessels about 100μm long and with diameters on order of 10μm. We show that the model of polymerization reflects well the role of fibrins in the c...
Platelet Motion near a Vessel Wall or Thrombus Surface in Two-Dimensional Whole Blood Simulations
Biophysical Journal, 2013
Computational simulations using a two-dimensional lattice-Boltzmann immersed boundary method were conducted to investigate the motion of platelets near a vessel wall and close to an intravascular thrombus. Physiological volume fractions of deformable red blood cells and rigid platelet-size elliptic particles were studied under arteriolar flow conditions. Tumbling of platelets in the red-blood-cell depleted zone near the vessel walls was strongly influenced by nearby red blood cells. The thickness of the red-blood-cell depleted zone was greatly reduced near a thrombus, and platelets in this zone were pushed close to the surface of the thrombus to distances that would facilitate their cohesion to it. The distance, nature, and duration of close platelet-thrombus encounters were influenced by the porosity of the thrombus. The strong influence on platelet-thrombus encounters of red-blood-cell motion and thrombus porosity must be taken into account to understand the dynamics of platelet attachment to a growing thrombus.
A simplified multi-particle collision dynamics method to simulate microvascular capillary blood flow
2014
Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom; Department of Engineering, University of Warwick, Coventry CV4 7AL; Centre for Complexity Science, University of Warwick, Coventry CV4 7AL, United Kingdom; Department of Physics, University of Warwick, Coventry CV4 7AL, United Kingdom; Institute for Solid State Physics and Optics, Wigner Research Center for Physics, Hungarian Academy of Sciences, P.O. Box 49, H-1525 Budapest, Hungary; Warwick Medical School, University of Warwick, Coventry CV2 2DX, United Kingdom; Department of Medicine, Office of Global Health, University of Yale School of Medicine, 15 York Street, 1074 New Haven, CT 06520 USA.
Mathematical Medicine and Biology, 2004
A model is developed to describe the formation of platelet thrombi in coronary-arterysized blood vessels. It involves interactions among a viscous, incompressible fluid; populations of non-activated and activated platelets; activating chemicals; and the vessel walls. Adhesion of platelets to the injured wall and cohesion between activated platelets is modelled using distributions of elastic links which generate stresses that can influence the fluid motion. The first version of the model presented involves two spatial scales: the microscale of the platelets and the macroscale of the vessel. A closure approximation is introduced that allows essential microscale behaviour to be computed while eliminating the necessity to explicitly track events on this scale. Computational methods are presented that meet the diverse challenges posed by the coupled nonlinear partial differential equations of the model and by the complex geometry of the constricted vessels in which the thrombosis simulations are carried out. Simulation results demonstrate that the model can produce thrombi that grow to occlude the vessel, that shear-stress exerted by the fluid on the thrombi can modify their subsequent growth and cause remodelling of their shape through smallscale local changes or large-scale structural breakup.