FINITE ELEMENT ANALYSIS OF PLATELET ACTIVATION AND CELL MECHANICS IN CIRCULATING TUMOR CELL ARREST

The progression of cancer from a localized tumor to a widespread metastatic disease is a complex and multifaceted process, making it cancer patients’ leading cause of death. The driving force behind this process is the presence of the Circulating Tumor Cells (CTCs), which break from the primary tumor site and spread through the bloodstream to colonize other organs (Fig. 1). The presence of CTCs in the blood is a strong indicator of the metastatic potential of a tumor. Despite their heterogeneity—since only a fraction can initiate secondary tumors—CTCs that persist in the bloodstream and evade immune surveillance are pivotal to metastatic progression. Metastasizing cancer cells can activate platelets at the primary site, increasing the local concentration of platelet microparticles (PMPs), that consequently can target CTCs regarding their number or affecting their metastatic potential presents a promising strategy for managing and preventing metastatic disease. Over the past decades, extensive research has explored the interaction between CTCs and platelets in the context of metastasis. Activated platelets play a crucial role in protecting CTCs from immune surveillance and hemodynamic shear forces, thereby enhancing their survival during circulation. Although the role of platelets in cancer metastasis is increasingly acknowledged, the exact mechanisms that initiate and sustain CTC–platelet interactions remain only partly understood. A deeper understanding of the molecular dynamics underlying CTC–platelet and CTC–vessel wall interactions is crucial for developing targeted strategies to disrupt these processes selectively, without compromising normal hemostasis or inflammatory responses and stiffness), the platelet size and stiffness, the ligand-receptor interaction intensity, on one side; and time in contact between the CTCs and platelet, conditions for the cell arrest, on the other side. This study applies a 2D computational model to investigate CTC dynamics in plasma flow through a parametric analysis of platelet adhesion, CTC size and stiffness, and ligand–receptor bond stiffness. Using a strong coupling method, solid–fluid interactions are solved simultaneously, supported by dynamic remeshing for stability. Ligand– receptor bonds are represented by 1D rope elements and experimentally measured adhesive forces with non-activated and thrombin-activated platelets are incorporated. This framework enables systematic evaluation of how geometrical and material properties, as well as platelet activation, influence CTC arrest and adhesion in circulation.