SUMMARY

Blood is a biological fluid that transports life-sustaining solutes throughout the body. Separately, blood can clot to stop hemorrhaging or obstruct the arteries to cause heart attacks or strokes. These critical pathophysiological processes rely on the participation of both microscale cells and nanoscale molecules subjected to hydrodynamics. In this thesis, we developed a coupled lattice-Boltzmann and Langevin-dynamics (LB-LD) approach, allowing for simulating blood flow and clotting processes with both cellular and molecular-level biophysical details. The research problems of interest to the thesis range from nano-drug delivery to high-shear thrombosis. For the transport of nano-drugs in microvessels, we demonstrated a particle size-dependent transition from Brownian-motion dominant dispersion to margination in microvessels. To study nanoparticle (NP) partition through microvascular bifurcations, a general particulate suspension inflow/outflow boundary condition is developed and used to discover a heterogeneous partition of the NP in response to the Zweifach-Fung (ZF) effect. To inform macroscale drug delivery applications through constitutive relations, we characterized the diffusion tensor of NP in sheared cellular blood over a wide range of shear rate and hematocrit. The nonlinear hemorheological scaling of the diffusivity was attributed to the RBC morphology change in principal directions. To elucidate the mechanisms for shear-induced platelet aggregation (SIPA), an in silico SIPA simulator informed by the status quo single-molecule measurements is developed. It is found that SIPA is a two-stage process involving in-flow agglomeration and capture of agglomerates to the surface. Transition from the lag time (LT) regime to rapid platelet accumulation (RPA) was attributed to the elevation of local VWF concentration and/or the VWF size. Some contradictory observations in the field of arterial thrombosis were addressed. This thesis provided a novel paradigm for simulating blood flow and clotting at both molecular- and cellular-scales. The multiscale in silico approach offers a cross-scale tool for exploring novel biophysical mechanisms for vascular diseases or other biophysical processes that are typically inaccessible to only single-molecule measurements, fluidic assays, or single-scale computational methods. Such new perspectives may lead to the discovery of novel therapies for life-threatening vascular diseases.