Dr. Aleeza Farrukh
UC Irvine
Abstract:
The ability of cells to efficiently communicate over organism-scale distances and across difficult-to-surmount biological barriers is one of the most important fundamental phenomena in biology. Within this context, a large body of work has demonstrated that intercellular communication is often mediated by cell-produced particles called extracellular vesicles (EVs). Despite the importance of EVs in various biological processes, there have been relatively few reports of successfully hijacking and artificially controlling EV-based cellular signaling pathways and then subsequently using such communication mechanisms to produce desirable outcomes in complex biological systems. Within this context, we have developed a powerful bioelectronic methodology that harnesses EV-mediated intercellular signaling for the on-demand regulation of cell fate from a distance. In particular, our approach employs mild electrical stimuli for actuating, regulating, and even reversibly cycling the production of EV populations with adjustable concentrations, size distributions, and protein contents from genetically engineered source cells. Moreover, our strategy allows for the directed electrical loading of biomolecular signaling cargo into designer EVs and for the subsequent electrical regulation of primary recipient cell differentiation by means of such EVs in situ. Together, the reported discoveries establish an exciting platform for fundamentally understanding EV-based cell-to-cell signaling mechanisms and may ultimately enable the development of transformative biomedical engineering technologies.