The biological basis, framework, and in vitro tool for the multiscale in silico model of SIPA. (A) Atherosclerosis creates a stenosis with wall shear rate to above 10 000 s⁻¹, leading to an acute arterial thrombus if the plaque cap ruptures. (B) At the exposed collagen surface, SIPA stems from nonactivated platelets and VWF. We virtually construct SIPA in a computational model including immobilized VWF dimers as blue beads on the surface, soluble VWF depicted as yellow strings, and GPIb-A1 bonds as red beads. (C) Framework of the multiscale in silico method.²⁶  VWFs and platelets are modeled in silico to match their biological counterparts based on in vitro measurements.^14,16  The dynamics of VWF strands and platelets suspended in the blood subjected to high shear rates are resolved through the coupling among lattice-Boltzmann method, Langevin-dynamics, and rigid body dynamics with fluid-structure interactions (FSI). Platelet and VWF binding kinetics are incorporated to the model, where the kinetic rates can be measured through single-molecular measurements such as biomembrane force probe,^50,51  optical tweezers,^20,21  atomic force microscopy,⁵²  etc. (D) A low-variability, high-throughput thrombosis-on-a-chip platform¹²  is used for the validation of the in silico results. Panels C and D partially adopt figures from previous publications^14,16,32  with permission.