Multiscale Computational Environment for Modeling Thrombus Development

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Multi-scale Computational Environment for
Modeling Thrombus Development
Fang QiAdvisor Prof. AlberDepartment of
MathematicsUniversity of Notre Dame
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Introduction
To prevent the loss of blood following a break in
blood vessels, components in blood and vessel
wall interact rapidly to form a thrombus to limit
hemorrhage. This hemostatic response is rapid
and regulated, since excessive and inappropriate
clotting reduces the patency of blood flow. The
biomedical importance of these reactions is
underscored by the severe and lethal consequences
resulting from failure and disregulation of the
hemostatic system.
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How blood clot forms
When a blood vessel is injured, platelets
suspended in the blood adhere to the damaged
tissue. Other platelets adhere to these
wall-adherent platelets and cohere with one
another to form a loose platelet plug or
aggregate that fills the hole and stems the loss
of cellular elements in the blood.
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The fibrin network
Normally fibrinogen is dissolved in a blood
plasma. It floats around, activating when a cut
or injury causes bleeding.
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The coagulation pathway

• Platelets are non-nucleated cells suspended in
  the blood plasma. In a healthy person, there are
  approximately 250 000 platelets per mm3 of blood.
  Yet because of their small size, platelets occupy
  less than 0.3 of the bloods volume.
• Platelets normally circulate in a dormant or
  unactivated state in which they do not adhere
  either to other platelets or to the intact blood
  vessel wall. A variety of plasma-borne chemical
  stimuli can bind to specific receptors on the
  platelets surface and thereby trigger the
  platelet activation process.
• Platelet activation entails
• the platelets surface membrane becoming sticky
  to other activated platelets
• the platelet beginning to release
  platelet-stimulating chemicals into the
  surrounding plasma
• the platelet changing morphologically from its
  rigid discoidal resting shape, to a more
  deformable approximately spherical form from
  which extend several long thin appendages known
  as pseudopodia (Weiss, 1975).

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• We propose to make the computational modeling of
  Thrombgenesis by the following components
• The Cellular Potts Model (CPM) for Platelet
  aggregation and coagulation. (Extending the
  chemical diffusion and fluid flow modules in the
  Compucell3D framework)
• Off-lattice Model of Coagulation and
  Fibrinolysis. (Use the energy method and M.C.
  simulation and Metropolis algorithm)
• Reaction kinetics of the coagulations
  process.(advection-diffusion system of
  equations)
• Hydrodynamics Model for the blood flow.(Navier
  -Stokes equations and CVTK)

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Experimental Models of Thrombogenesis By
Dr.Elliot Rosens lab, Indiana University School
of Medicine

• A flow chamber will be used to test the
  predictions of the computational models as
  described above.
• The bottom surface can be covered with various
  thrombogenic surfaces including endothelial cells
  grown in the culture dish or matrix proteins that
  can be used to coat the dishes.
• Plasma flows from an input reservoir to the
  input port of the transparent block, through the
  channel cut in the membrane and exits through the
  output port.
• A syringe pump in line with the outflow tubing
  is used to control flow rates through the chamber