Biophysics of the curvature sensing of septin cytoskeletal filaments

The ability of cells to sense and respond to their shape is key to many cellular functions. Septins are GTP-binding nanometer-scale proteins that sense and localize to sites of positive micron-scale membrane curvature in Eukaryotic cells from yeast to humans. The underlying physical principles that control this process remain poorly understood. Septin assembly begins with the binding of short nanometer-sized rod complexes, referred to as septin octamers, to the membrane. Upon binding, these octamers can diffuse and anneal (polymerize) to form larger filaments and ultimately self-organize into assemblies that can span several microns. However, it is unclear how each of these events, and hence septin self-organization as a whole, are influenced by the membrane’s curvature. Here we examine the biophysical basis of curvature sensing by septins at each of these steps, using a combination of single-molecule imaging, scanning electron microscopy, biophysical modeling, and simulations. We find that the membrane curvature influences the kinetics of binding/unbinding of septin complexes, their diffusion on the membrane as well as their length distribution and self-organization. These data suggest that curvature sensing by septins operates at multiple length scales, rather than simply at the scale of a single protein/membrane and it provides a framework for understanding the interplay between curvature sensing and self-organization of septin filaments.

Related Publications:

Shi, W., Cannon, K. S., Curtis, B. N., Edelmaier, C., Gladfelter, A. S., & Nazockdast, E. (2023). Curvature sensing as an emergent property of multiscale assembly of septins. Proceedings of the National Academy of Sciences, 120(6), e2208253120.