(C-84) Shear-Mediated Platelet Adhesion Dynamics: Correlating In Silico with In Vitro Results

Introduction:: Platelet adhesion to blood vessel walls and platelet-platelet aggregation in shear flow is essential in initiating blood coagulation and prompting clot formation in vascular disease processes and prosthetic cardiovascular devices. We developed a combined Dissipative Particle Dynamics (DPD)-Coarse Grained Molecular Dynamics (CGMD) multiscale model (MSM) [1-2] to continuously evolve platelet structures, describe flow-induced platelet mechanotransduction, synergistically activate platelets, and aggregate, and adhere them to blood vessels. We modeled platelet flipping behaviors and validated with in vitro microchannel experiments [3-4].

Materials and Methods:: Our MSM model, which describes the nanoscale mechanotransduction and biophysics of deformable CGMD platelets under viscous blood flow, was adapted to describe platelet flipping and adhesion over von Willebrand Factor (vWF) in a channel with DPD particles at 15-45 dyne/cm² (Fig. 1A). The platelet’s bilayer membrane has a total of 67,004 particles, with 16,751 particles designated as GPIbα receptors, with a curvature-based probability distribution function (Fig. 1B) [5]. vWF binding sites were fixed on the blood vessel wall, with an average distance between two binding sites of 52 nm. vWF particle wall density was then decreased uniformly to study the effect of vWF distribution on adhesion dynamics. Simulations were validated with in vitro dynamics extracted from machine learning (ML)-guided segmentation of platelets flipping in microchannels [4].


Results, Conclusions, and Discussions:: Our MSM model described the biophysical properties for platelet adhesion and thrombus down to the nm-length and ps-time scales. Angular velocity during platelet flipping was quantified in vitro and in silico under shear stresses of 15, 30 and 45 dyne/cm² (Fig. 1F-G). Our multiscale adhesion model can provide comprehensive information on the GPIbα-vWF bonds acting on the platelet. At dimensionless time 0, the platelet approaches 𝜋/2 and the total bond force is 800 pN, corresponding to 200 GPIbα-vWF bonds (Fig. 1H-I). Prior to dimensionless time 0, bond number decreases proportionally with a decrease in shear stress. We observed an asymmetrical pattern in the simulated results as defining ω₁: [𝜋/3, 𝜋/2] and ω₂: [𝜋/2, 2𝜋/3] (Fig. 1E). For each shear stress, the lift-off period is consistently longer than the following reattachment period. Ongoing simulation shows lower vWF density corresponds to lower GPIbα-vWF bonds and a higher chance of wobbling and detaching behaviors, which were corroborated in vitro (Fig. 1K).


Acknowledgements (Optional): : This project is supported by the NHLBI (5U01HL131052, DB) and the SUNY-IBM Consortium (88003, YD), and computational resources on the AiMOS supercomputer.

References (Optional): : [1] Zhang, P., et al, J Biomech, 2017, 50:26-33. [2] Gupta, P. et al., Cell Mol Bioeng, 2019, 12:327-43. [3] Zhang, Z. et al., Comput Med Imaging Graph, 2021, 89:101895. [4] Sheriff, J. et al. Ann Biomed Eng, 2021. [5] Wang, P. et al. Ann Biomed Eng, 2023.