Dr. Susan N. Thomas, Chair (ME), Advisor
Dr. J. Brandon Dixon (ME)
Dr. Todd Sulchek (ME)
Cell adhesion chromatography system for biophysical to biochemical analysis of human colon cancer metastasis through the vasculature.
Cell adhesion under the influence of hemodynamic forces in the vasculature plays a pivota role in physiological and pathophysiological phenomena, including immune cell recruitment, stem cell homing, and cancer metastasis. A key class of adhesion molecules involved in these processes is selectin, which initiate cell-cell interactions by slowing circulating cells down relative to bulk flow to facilitate firm adhesion, suggesting interventions directed at attenuating or increasing selectin adhesion could provide therapeutic means to tune cell homing processes. The selectin binding activity of cells over long time and length scales, which best recapitulates the cell adhesion challenges experienced within the circulatory system to predict the functional capacity of cells to eventually achieve firm adhesion and extravasate, has not been determined. To address this issue, we developed a so-called “cell adhesion chromatography” system based on a microfluidic device to investigate cell adhesion behavior to selectins over long time and length scales. Our system is equipped with a feature that enables uniform cell contact the selectin-coated substrate by exploiting Stoke’s flow. Using the system, we performed residence time distribution experiments with a pulse input of cells at different shear stresses by imaging them within a field of view at prescribed distances from the inlet. Residence time distribution plots were then generated and compared between healthy (human monocyte) and malignant (human colon carcinoma) cells. Differences in the functional capacity of each cell type to sustain interactions with selectins were observed. In summary, we have developed a microfluidic-based system that provides a new way to investigate the efficiency of selectin-mediated cell adhesion for the interrogation of selectin binding biophysics of whole cells in fluid flow and for the screening of adhesion-modulating drugs for eventual translation into therapeutic applications.