Abstract

Organ-on-Chip Systems to Probe Extracellular Vesicle Transport Across Biological Barriers

Steven C. George, Professor, University of California, Davis

Extracellular vesicles (EVs) are small (50-150 nm diameter) composite particles secreted by cells and comprised of a lipid-based membrane surrounding an aqueous core.  The membrane and core can each incorporate a wide range of molecules (e.g., proteins, nucleic acids) that can impact cellular function; thus, EVs can impact in vivo biology, but have also generated significant excitement for their potential theranostic (therapeutic and diagnostic) applications in cancer. How EVs are transported (convection, diffusion, and binding) across biological barriers including the vascular endothelium and extracellular matrix is poorly understood.  Our early work demonstrates that a subpopulation of EVs are transported across the endothelium using receptor-mediated transcytosis, and predominantly by convection (not diffusion) through the extracellular space. During transport through the ECM, the EVs can bind (and unbind) to form a spatial gradient which may have biological implications for cell migration and tumor progression. Examination of EV transport across biological barriers will not only enhance our understanding of the dynamic tumor microenvironment, but also provide the framework to design artificial nanovesicles as novel drug delivery vehicles.