PB0879 - Structural Mechanisms and Kinetics of Blood Clot Contraction from in silico Modeling

Background: Blood clot contraction is an important pathophysiologic biomechanical mechanism of hemostasis and thrombosis. There are no computational models that can be used to explore the mechanism(s) of clot contraction.

Aims: To develop a Stochastic Reaction Diffusion Dynamics (SRDD) model of blood clot contraction in silico capable of providing mechanistic insights and parameterize the clot contraction kinetics to complement the experimental data.

Methods: The proposed SRDD model simulates 3D contraction of a fibrin clot containing activated platelets with a high spatial and temporal resolution. It involves a branched network of fibrin fibers (flexible cylinders) and activated platelets (spherical particles) with extensions mimicking thin cellular protrusions (filopodia). The model combines Langevin Dynamics of the growth and shortening of the filopodia and stretching and bending of fibrin fibers with a Monte-Carlo technique to account for the experimentally observed growth and shortening of the filopodia and interactions between the filopodia and fibrin fibers.

Results: We parameterized the SRDD model and compared the results of simulations obtained based on this computational model with the experimental kinetic data of clot contraction in platelet-rich plasma (see Figure). The experimental and simulated curves characterizing the kinetics of clot contraction agree very well, which validates our computational modeling approach. We also obtained very good agreement for the speed of platelet displacement; the size of platelet aggregates; and the amount of fibrin accumulated on platelets.

Conclusion(s): The newly developed computational model of clot contraction can be used to explore the microscopic structural mechanism(s) of clot contraction and predict effects on clot contraction of variations of platelet count and functionality, cellular and molecular blood composition, various medications, etc.