Modelling thrombosis using dissipative particle dynamics method

• Published in: Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences physical, and engineering sciences, 2008-09, Vol.366 (1879), p.3265-3279
• Main Authors: Filipovic, N, Kojic, M, Tsuda, A
• Format: Article
• Language: English
• Subjects: Adhesion; Aggregation; Agonists; Arterial Occlusive Diseases - physiopathology; Blood; Blood Physiological Phenomena; Blood Platelets; Blood vessels; Computer Simulation; Dissipative Particle Dynamics; Hemorheology - methods; Humans; Modeling; Modelling; Models, Cardiovascular; Particle interactions; Platelet Activation; Platelet aggregation; Platelets; Thrombosis; Thrombosis - physiopathology
• ISSN: 1364-503X; 1471-2962
• DOI: 10.1098/rsta.2008.0097

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 colloidal fluid, but significantly larger than the size of atoms such that, in contrast to the molecular dynamics approach, detailed atomic level analysis is not required. Results. To test this model, we simulated the deposition of platelets onto the wall of an expanded tube and compared our computed results with the experimental data of Karino et al. (Miscrovasc. Res. 17, 238-269, 1977). By matching our simulations to the experimental results, the platelet aggregation/adhesion binding force (characterized by an effective spring constant) was determined and found to be within a physiologically reasonable range. Conclusion. Our results suggest that the DPD method offers a promising new approach to the modelling of platelet-mediated thrombosis. The DPD model includes interaction forces between platelets both when they are in the resting state (non-activated) and when they are activated, and therefore it can be extended to the analysis of kinetics of binding and other phenomena relevant to thrombosis.