Subdomains of endophilin can drive membrane remodeling and facilitate controlled membrane scission.

The NBAR-domain-containing protein endophilin, a major player in many endocytic pathways, has offered considerable insight into Bin/amphiphysin/Rvs (BAR)-domain-driven membrane remodeling. However, understanding how the different subdomains of endophilin interact and how they sense and generate negative Gaussian curvature remains an unanswered question, with significant implications for the mechanisms and regulation of unconventional endocytic pathways. Using coarse-grained molecular dynamics simulation, we demonstrate the synergistic remodeling capabilities of the NBAR remodeling unit, as well as its ability to sort to and generate membrane regions with negative Gaussian curvature. We find that the assembly of NBAR scaffolds at regions of negative Gaussian curvature facilitates membrane hemifission in dynamic bud formation. These insights provide an additional role for endophilin scaffolds in endocytosis and emphasize the importance of developing new ways to study negative Gaussian curvature.