Multiscale Modeling of Shear-Dependent Tumor Cell Adhesion

Circulating tumor cells (CTCs) interact with the vascular endothelium under hemodynamic forces that influence where metastatic seeding occurs. Wall shear stress (WSS) has been shown to regulate adhesive signaling, yet its mechanistic role in shaping spatial patterns of CTC arrest within complex vascular networks remains poorly understood. In this work, we present a three dimensional multiscale simulation framework that couples tissue scale blood flow with receptor ligand adhesive dynamics whose kinetics depend on local WSS. We evaluate three modes of WSS regulation, including modulation by WSS magnitude, modulation by the local spatial gradient of WSS, and modulation by peak upstream WSS gradient within a region of influence. Using physiologically realistic vessel geometries and flow conditions, we track thousands of CTCs across tissue scale vascular networks using a high throughput adaptive refinement strategy executed on the Aurora supercomputer. Across a curved microvessel and a reconstructed bioprinted double bifurcation network, WSS magnitude dependent adhesion produces strong spatial biases in CTC arrest. In the bioprinted network, inclusion of WSS regulated adhesion leads to a thirty one fold increase in active receptor engagement in the lower entry fork compared to a non WSS modulated baseline, consistent with experimentally observed regional enrichment. These results demonstrate that local WSS profiles act as a physical driver of preferential CTC attachment and motivate inclusion of shear regulated adhesion in predictive models of metastatic transport.