A Multiscale Model for Recruitment Aggregation of Platelets by Correlating with In Vitro Results

Abstract

Introduction

We developed a multiscale model to simulate the dynamics of platelet aggregation by recruitment of unactivated platelets flowing in viscous shear flows by an activated platelet deposited onto a blood vessel wall. This model uses coarse grained molecular dynamics for platelets at the microscale and dissipative particle dynamics for the shear flow at the macroscale. Under conditions of relatively low shear, aggregation is mediated by fibrinogen via αIIbβ3 receptors.

Methods

The binding of αIIbβ3 and fibrinogen is modeled by a molecular-level hybrid force field consisting of Morse potential and Hooke law for the nonbonded and bonded interactions, respectively. The force field, parametrized in two different interaction scales, is calculated by correlating with the platelet contact area measured in vitro and the detaching force between αIIbβ3 and fibrinogen.

Results

Using our model, we derived, the relationship between recruitment force and distance between the centers of mass of two platelets, by integrating the molecular-scale inter-platelet interactions during recruitment aggregation in shear flows. Our model indicates that assuming a rigid-platelet model, underestimates the contact area by 89% and the detaching force by 93% as compared to a model that takes into account the platelet deformability leading to a prediction of a significantly lower attachment during recruitment.

Conclusions

The molecular-level predictive capability of our model sheds a light on differences observed between transient and permanent platelet aggregation patterns. The model and simulation framework can be further adapted to simulate initial thrombus formation involving multiple flowing platelets as well as deposition and adhesion onto blood vessels.

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Acknowledgements

This publication was made possible by grants from the National NIH U01 HL131052-014 (PI: Danny Bluestein, Co-Investigators: Yuefan Deng, Marvin J. Slepian). The simulations in this study used the XSEDE computing resource award DMS150011 at the SDSC Comet supercomputer (PI: Peng Zhang) and LI-Red supercomputer, Stony Brook University.

Conflict of interest

Prachi Gupta, Peng Zhang, Jawaad Sheriff, Danny Bluestein and Yuefan Deng declare that they have no conflict of interest.

Human Studies

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study. No animal studies were carried out by the authors for this article.

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Gupta, P., Zhang, P., Sheriff, J. et al. A Multiscale Model for Recruitment Aggregation of Platelets by Correlating with In Vitro Results. Cel. Mol. Bioeng. 12, 327–343 (2019). https://doi.org/10.1007/s12195-019-00583-2

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Keywords

  • Multiscale modeling
  • Hybrid force field
  • Contact area
  • Detaching force