Title : Signal amplification in molecular cascades on cell surfaces
Abstract:
Molecular cascades that analyze pairs or triplets of surface markers on individual cells in a manner of Boolean logic gates are based on chemical reaction networks comprising oligonucleotide-antibody conjugates and partially complementary oligonucleotides. While traditional methods to positively select cells are based on a single marker, these cascades can be used to isolate, in a single step, a narrower subpopulation based on the presence of two or more surface markers. In our original design, oligonucleotide components irreversibly flowed from one cell surface marker to the next one, driven by increases in complementary interactions between oligonucleotides. Therefore, the magnitude of the final signal was always determined by the cell surface marker that was least abundant on the surface of each cell. We now improve our design to demonstrate, on two examples, the signal amplification from a less to a more abundant cell surface marker, where one component serves as a catalyst to activate multiple downstream elements, while itself being renewed by sacrificial solution-state component. We expect this new function to enable increasingly complex Boolean analysis of cell surfaces.
