BAR scaffolds drive membrane fission by crowding disordered domains

Wilton T. Snead; Wade F. Zeno; Grace Kago; Ryan W. Perkins; J Blair Richter; Chi Zhao; Eileen M. Lafer; Jeanne C. Stachowiak

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/276147 doi: bioRxiv preprint the formation of membrane micelles, which are similar in morphology to the hemifusion intermediates that form during membrane fission (Campelo et al., 2012; Frolov et al., 2015) . Notably, vesicles in these experiments were composed primarily of the lipid DOPC, which has a lower bending rigidity than physiological membranes (Dimova, 2014) . In contrast, when we increased bilayer rigidity by replacing DOPC with the substantially more rigid, fully-saturated lipid DPPC (Dimova, 2014; Lee et al., 2001) , the average diameter of fission products increased to approximately 50 nm at 50 nM of FCHo1-FL, consistent with bilayer vesicles (Fig. S5E-G) . Collectively, these studies show that, despite their gentle curvature, F-BAR scaffolds are also capable of collaborating with disordered domain crowding to drive efficient membrane fission, producing highly curved vesicles. These findings suggest that the ability of BAR domains to assemble into scaffolds that concentrate disordered domains, regardless of their intrinsic structural curvature, is the key requirement for membrane fission.