(469g) Self-Assembly of Generic Scaffolding Proteins on Biologically Relevant Membranes

Bin/Amphiphysin/Rvs (BAR) proteins are a family of proteins responsible for initiating and driving membrane deformation orders of magnitude larger than a single protein. While protein-mediated membrane remodeling is key to many cellular processes, the suggested mechanism used by BAR proteins is through dense protein scaffold. Simulations of BAR domains can improve our understanding of membrane remodeling by adding detail to the protein self-assembly precursor to large-scale deformation. We develop a mesoscopic phenomenological model explicitly representing each protein/BAR domain and the membrane. A generic representation is used which is capable of modeling the full spectrum of the BAR family from positively curved N- and F-BAR to negatively curved I-BAR domains. The generic representation of the protein may include explicit representation of full length protein or fused intrinsically disordered domains. Previous mesoscopic models of BAR domains that rely on protein fields have been incapable of capturing the effects of other domains in addition to the BAR domain. Our simulation results show a variety of protein self-assembly and curvature sensing behavior dependent on membrane shape (e.g. tubule or vesicle), protein intrinsic curvature (e.g. N- vs. F-BAR-like proteins), and presence of full-length protein vs. isolated BAR domain. By studying various geometries and protein representations, we performed a comprehensive study of geometric and full-length crowding effects that play a critical role in protein scaffold formation.