COMPUTATIONAL MODELING AND PARAMETRIC STUDY OF CIRCULATING TUMOR CELL (CTC) MOTION AND ATTACHMENT IN CAPILLARIES WITH PLATELET INTERACTION AND ACTIVATION

Metastasis involves the dissemination of circulating tumor cells (CTCs) from the primary tumor, their survival in the bloodstream, and eventual colonization of distant organs. Adhesive interactions with platelets, leukocytes, and endothelial cells are critical to CTC survival and extravasation. Platelet adhesion enhances CTC viability and promotes metastasis. To investigate the biomechanical conditions governing CTC arrest, we developed a computational platform within the PAK software, integrating 2D axisymmetric solid-fluid models. This framework evaluates CTC transit through capillaries under physiological conditions and examines how capillary pressure gradients, CTC size and stiffness, and platelet size influence arrest dynamics. A parametric analysis was conducted to assess the effects of platelet number, CTC mechanical properties, and ligand-receptor bond stiffness on CTC trajectory, axial positioning, and endothelial adhesion. Both resting and thrombin-activated platelets were modeled, incorporating experimental adhesion force data via 1D finite element truss elements to simulate ligand-receptor interactions. The study establishes quantitative relationships between cellular and molecular parameters and the mechanical thresholds for CTC arrest, providing insights into early metastatic events and improving predictive models of metastasis progression.