Dynamic adhesion characterization of cancer cells under blood flow-mimetic conditions: effects of cell shape and orientation on drag force

Abstract

Cell adhesion to and detachment from the endothelium plays an essential role in numerous biological processes such as cancer cell metastasis, cell migration, and cell–cell communication. However, little is known about the effect of cell shape and orientation on the drag force leading to cell detachment. To further investigate these factors, we cultured cancer cells in a microfluidic channel, and recorded the shape and orientation of the cells under constant fluid flow rate. Results showed that cell morphology varied dynamically with respect to time. In particular, we discovered two distinct shapes of cells at the moment of detachment: the circular shape, and the elongated shape whose long axis is perpendicular to the flow. Based on the experimental observations, we designed and reconstructed two cellular solid models (a hemispherical model and an elongated model) to calculate the drag force using a finite-element method. The hemispherical model yielded much higher pressure drag force than that of the elongated models irrespective of orientation, though the total drag force of the hemispherical model was slightly lower. We also examined the effect of the orientation on the drag force using five different orientations to the flow. The cells of which the long axes were perpendicular to the flow exhibited larger pressure drag force than cells oriented in other directions, though the friction drag force was comparable. In summary, when cells detach from the surface, the fraction of the pressure force becomes larger, demonstrating the determinative role of cell adhesion and/or detachment. Significantly, our observation that two cancer cell subpopulations exist exhibiting different morphological dynamics and required drag forces for detachment implies redundant mechanisms for cancer cells to achieve the transition from the adherent type to the circulating type during metastasis.