Susan Thomas, Ph.D. (Georgia Institute of Technology)
Andrés García, Ph.D. (Georgia Institute of Technology)
Wilbur Lam, Ph.D. (Georgia Institute of Technology & Emory University)
John McDonald, Ph.D. (Georgia Institute of Technology)
Cheng Zhu, Ph.D. (Georgia Institute of Technology)
ELUCIDATING THE CONTRIBUTIONS OF CELLULAR AND MICROENVIRONMENT CHARACTERISTICS ON CELL ADHESION PROCESSES IN FLOW
Circulating cell recruitment is critical to a variety of physiological and pathophysiological processes and occurs amidst the high shear environment of the vasculature via a multistep rolling to firm adhesion cascade. Cells initially engage the vascular endothelium through interactions between endothelial-presented selectins and their corresponding ligands presented by circulating cells. These interactions precede firm adhesion and arrest and eventually transmigration across the endothelium for tissue infiltration. Since many cell subtypes including leukocytes and metastatic cancer cells employ this mechanism to facilitate their escape the vasculature, understanding differences in cell-subtype adhesive behavior can inform the development of targeted therapeutics that interfere with metastatic cell transport, while leaving physiologically important immune cell recruitment mechanisms intact. As such, the overall objective of this proposal is to explore how selectin-mediated adhesion 1) is regulated by the biochemical and biophysical microenvironment of the vasculature and 2) varies among different cell subtypes. Through the use of in vitro fluidic methodologies in conjunction with innovative single-cell analyses we expect to elucidate key differences in the selectin-dependent adhesive behavior of metastatic versus leukocytic cells in order to inform targeted drug development and dosing strategies for the cell-subtype selective interference of cell adhesion.