(283d) A Suspension Cell-based Interaction Platform for Interrogation of Membrane Proteins
AIChE Annual Meeting
2020 Virtual AIChE Annual Meeting
AIChE Futures: New Directions in Chemical Engineering Research II (Invited Talks)
Tuesday, November 17, 2020 - 2:00pm to 2:15pm
The majority of clinically approved therapeutics target membrane proteins (MPs), highlighting the need for tools to study this important category of proteins. To overcome limitations with recombinant MP expression, whole cell screening techniques have been developed that present MPs in their native conformations. Whereas many such platforms utilize adherent cells, here we introduce a novel suspension cell-based platform termed âbiofloatingâ that enables quantitative analysis of interactions between proteins displayed on yeast and MPs expressed on mammalian cells, without need for genetic fusions. We characterize and optimize biofloating and illustrate its sensitivity advantage compared to an adherent cell-based platform (biopanning). We further demonstrate the utility of suspension cell-based approaches by iterating rounds of magnetic-activated cell sorting (MACS) selections against MP-expressing mammalian cells to enrich for a specific binder within a yeast-displayed antibody library. Overall, biofloating represents a promising new technology that can be readily integrated into protein discovery and development workflows.