The Physical Basis of Curvaure Sensing by Septins

The ability of the cell to sense and change its shape is key to many processes, including membrane trafficking, endocytosis and morphogenesis. Septins are GTP-binding nanoscopic proteins that localize to sites of micrometer-scale membrane curvature. Upon binding, the septins diffuse and anneal (polymerize) to form longer filaments and assemblies that span the membrane surface. The relationship between the curvature-dependent binding of septins and their self-assembly remains unclear. Here we use a combination of biophysical modeling and simulations, single molecule imaging and scanning electron microscopy to study the interplay between membrane’s curvature and the different processes involved in septin assembly, including septins’ membrane association/dissociation, diffusion and polymerization rates. Our modeling and experimental results suggest that curvature sensing by septins is qualitatively changed with the structure and density of the bound septins and, thus, operates at multiple length- and time-scales.