  Occlusive thrombosis in arteries causes heart attacks and strokes. The rapid
growth of thrombus at elevated shear rates (~10,000 1/s) relies on
shear-induced platelet aggregation (SIPA) thought to come about from the
entanglement of von Willebrand factor (VWF) molecules. The mechanism for SIPA
is not yet understood in terms of cell- and molecule-level dynamics in
fast-flowing bloodstreams. Towards this end, we develop a multiscale
computational model to recreate SIPA in silico, where the suspension dynamics
and interactions of individual platelets and VWF multimers are resolved
directly. The platelet-VWF interaction via GP1b-A1 bonds is prescribed with
intrinsic binding rates theoretically derived and informed by single-molecule
measurements. The model is validated against existing microfluidic SIPA
experiments, showing good agreement with the in vitro observations in terms of
the morphology, traveling distance, and capture time of the platelet
aggregates. Particularly, the capture of aggregates can occur in a few
milliseconds, comparable to the platelet transit time through pathologic
arterial stenotic sections and much shorter than the time for shear-induced
platelet activation. The multiscale SIPA simulator provides a cross-scale tool
for exploring the biophysical mechanisms of SIPA in silico that are difficult
to access with single-molecule measurements or micro-/macro-fluidic assays
only.
