The mechanical basis for single amphipathic helix engagement with membranes

Septins are a class of cytoskeletal proteins that can sense and communicate details about micron-scale curvature based on their binding to cellular membranes. Studies show that amphipathic helix (AH) domains on the protein are indispensable for the ability of these nanoscale proteins to probe micron-scale curvatures. Yet, the underlying mechanochemical interactions that modulate this curvature sensing remains ambiguous. One barrier is the difference in time scale(s) between atomistic, coarse-grained, and continuum simulations when compared to in vivo or in vitro experiments. I will present research into how AH-domains interact with cellular membranes at the atomistic scale. Our preliminary results suggest that the folded, helical form of the AH-domain leads to stable membrane association, while the unfolded form leads to dissociation from the membrane. Additionally, our results suggest that the structure of AH-domain-membrane interface seems to be driven by electrostatic interactions.