Design and Synthesis of Bioinspired Membrane Curvature Sensors

Septin proteins are the only known micron-scale curvature sensors in eukaryotes. These proteins assemble cooperatively and use motifs, such as amphipathic helices, to bind the membrane and detect curvature through mechanisms that are largley unknown. Despite their central role in both health and diverse disease states, the nature of the lipid defects sensed by septins at shallow curvatures and their physical basis for sensing remain unknown. We show how the structural and physical features of septins is exploited in the design of syntethic micron-scale curvature sensors. By reverse-engineering septins, we elucidate the mechanism of septin-mediated curvature sensing and engineer septin-mimetic curvature sensors that can be triggered to recognize multiple curvatures and transduce reactions as a response to the sensing event.