Curvature-induced margination and adhesion of circulating tumor cells in microvessels

The selective retention and adhesion of circulating tumor cells (CTCs) in microvessels are key biophysical events during early hematogenous metastasis. Although experiments have reported preferential CTC adhesion at vascular bends, the underlying mechanical mechanism remains unclear. Here, an immersed boundary–lattice Boltzmann method coupled with a probabilistic receptor–ligand adhesion model is used to simulate CTC migration and adhesion in three-dimensional curved microvessels. The effects of arch height, hematocrit, CTC membrane bending stiffness, and initial CTC position are systematically examined. Vessel curvature displaces the local velocity peak toward the wall facing the local center of curvature and reorganizes the red blood cell (RBC) distribution. The resulting lateral exclusion promotes CTC margination and spatially selective wall contact. Increasing arch height modifies the local flow structure and wall-contact probability, thus regulating adhesion strength and adhesion-enriched regions. Hematocrit alters the near-wall cell-free layer and the intraluminal shear-rate distribution, while membrane bending stiffness controls deformation-dependent wall contact and bond accumulation. The initial lateral position sets the distance from the near-wall low-velocity layer and consequently determines the onset of margination and the final adhesion site. Overall, CTC adhesion in curved microvessels is governed by the coupled effects of shear flow, RBC redistribution, cell margination, and near-wall residence time. These findings clarify the biomechanical origin of curvature-induced CTC adhesion and provide a hemodynamic basis for assessing metastasis-prone microvascular regions.