An adaptive physics refinement framework to investigate red blood cells’ impact on adhesive tumor cell transport

Abstract

Red blood cells play a dominant mechanical role in blood flow and strongly influence the transport and arrest of circulating tumor cells during metastasis. Circulating tumor cells (CTCs) are subject to physical interactions with blood components and adhesive interactions with endothelial cells, both of which critically influence their margination and likelihood of arrest. However, the impact of red blood cells (RBCs), the most abundant cellular component of blood, on CTC adhesion remains understudied. Multiscale computational methods provide a unique platform for investigating RBC–CTC interactions by enabling precise parameter control and quantitative analysis. Nevertheless, traditional explicit simulations have been limited in physiological relevance due to the high computational demand of modeling sub-micron scale adhesion dynamics in millimeter-scale vasculature. Here we employ and extend an adaptive physics refinement (APR) framework that couples a high-resolution region of interest to a coarsely resolved bulk fluid domain. We incorporate both RBC interactions and adhesive dynamics in the high-resolution region, enabling simulation of adhesive CTC transport with drastically reduced computational memory. Simulation results demonstrate that RBC–CTC interactions and RBC orientation significantly impact CTC trajectory and adhesive behavior. Compared to traditional explicit fluid-structure-interaction methods, the APR approach results in an order of magnitude decrease in memory usage, enabling analysis of larger vessel domains pertinent to metastasis. By providing a computationally efficient tool for simulating RBC interactions and adhesive dynamics, the extended APR framework paves the way for systematic investigation of tumor cell transport with increased physiological relevance.