Modeling cell clusters and their near-wall dynamics in shear flow

Abstract

The studies that compare the metastatic potential of tumor cell clusters in microcirculation to that of single tumor cells show that the clusters contribute significantly to metastasizing. The metastatic potential is conditioned by the presence of the cancer cells near vessel walls. Detailed understanding of dynamical behavior of clusters near the vessel walls can thus elucidate the process of adhesion. We have developed a biomechanical model of cell clusters capable of simulating both strong and weak adhesion among the cells in the cluster in various spatial configurations. We have validated the model on data from cell separation experiments. The developed model has been used to study near-wall dynamics in shear flow with focus on cluster–wall contact. To quantify the presence of cells near walls, we have evaluated metrics involving time of contact and contact area of clusters tumbling and rolling near the wall. The computational results suggest two trends: First, more elastic clusters and clusters of weakly adhesive cells have decreased cluster–wall contact to the walls than rigid clusters or clusters composed of strongly adhesive cells. Second, more spherical cluster shapes tend to drift away from the walls, thus decreasing the wall contact time.