Multiscale Modeling

Modeling dynamic platelet response to flow conditions

Elucidation of the complex interactions between living tissues and mechanical stimuli, as represented by the vexing problem of shear-mediated platelet activation and resultant thrombosis, can be realized by innovative multiscale modeling (MSM) approaches.

The coupling of the disparate spatial-temporal scales between the macroscopic transport and the molecular level events represents a major modeling and computational challenge. Continuum approaches can be effectively utilized only down to the micron level and are limited in their ability to cover the smaller molecular mechanisms such as filopodia formation during platelet activation. Utilizing molecular dynamics (MD) to cover the multiscales involved is computationally prohibitive.

We have developed an integrated MSM methodology that addresses the mechano-biological “linkages,” and cover the vast range of spatiotemporal scales involved:

  • Dissipative Particle Dynamics (DPD) model of viscous blood flow, interfaced with a bottom Coarse Grained Molecular Dynamics (CGMD) model of platelets. This integrated model simulates their activation process via mechanotransduction pathways
  • Platelets are composed of internal structural and functional components (bilayer membrane, microtubules, cytoplasm, and cytoskeleton)
  • Fully interactive interface between the top and bottom models through an hybrid force field interface and a multiple time stepping (MTS) scheme for handling the temporal disparity
  • Validation of computational models with in vitro experiments of platelet shape change and motion, performed using the hemodynamic shearing device (HSD) and microchannels. Images are obtained using scanning electron microscopy (SEM) and DIC microscopy with a high framerate sCMOS camera