Modeling of Tumor Cell Adhesion, Extravasation, and Sorting in a Microvascular System.

摘要

Blood flow dynamics in microvessels dictate the transport modes of circulating tumor cells (CTCs) and, consequently, influence their metastatic potential. While extensive biochemical and biological studies have advanced our understanding of CTC metastasis, precise experimental measurements and accurate theoretical predictions of its mechanical underpinnings remain limited. To address this gap, this chapter presents numerical modeling of CTC extravasation from the bloodstream, encompassing the critical steps of adhesion and transmigration. The simulations reveal that CTCs preferentially adhere to regions of positive curvature in curved microvessels, a phenomenon attributed to favorable wall shear stress gradients. Subsequent analyses underscore the significant influence of blood's particulate nature on CTC adhesion in these vessels. Moreover, red blood cell (RBC) aggregates enhance CTC adhesion by imparting an additional wall-directed force. Furthermore, modeling a single cell traversing a narrow slit-to mimic transmigration-demonstrates that alterations in cell shape and surface area play a more pivotal role than cell elasticity in enabling passage through such constrictions. Finally, numerical simulations of CTC-RBC separation in microfluidic devices, featuring varied microcolumn geometries and arrangements under diverse flow regimes, were presented to optimize the sorting system's design.