CBE Seminar: Septin Proteins Sense Membrane Curvature by Their Multiscale Assembly

Abstract:The ability of cells to sense and communicate their shape is central to many of their functions. Yet, how cells sense and respond to geometric cues remains poorly understood. Septins are GTP-binding proteins that localize to sites of micrometer-scale membrane curvature. Assembly of septins is a multistep and multiscale process, but it is unknown how these discrete steps lead to curvature sensing. Here, we experimentally examine the time- dependent binding of septins at different curvatures and septin bulk concentrations. These experiments unexpectedly indicated that septins’ curvature preference is not absolute but rather is sensitive to the combinations of membrane curvatures present in a reaction. To understand the physical underpinning of this result, we developed a kinetic model that connects septins’ self-assembly and curvature-sensing properties. When combined, the work indicates that septin curvature sensing is an emergent property of the multistep, multiscale assembly of membrane-bound septins. As a result, curvature preference is not absolute and can be modulated by changing the physicochemical and geometric parameters involved in septin assembly, including bulk concentration and the available membrane curvatures. While much geometry-sensitive assembly in biology is thought to be guided by intrinsic material properties of molecules, this is an important example of how curvature sensing can arise from multiscale assembly of polymers.  

Septin assembly is in part determined by the drag of the bound septin filaments. Previous modeling studies have considered the dynamics of a single filament on fluid planar membranes. We extend these studies to the more physiologically relevant case of a single filament moving in a spherical membrane. We use slender-body theory to compute the filament’s parallel, perpendicular and rotational drag coefficients as a function of its length, membrane radius and membrane viscosity in freely suspended and supported bilayers as models for the biological cell. We show that the boundedness of spherical geometry gives rise to flow confinement effects that increase in strength with increasing the ratio of the filament’s length to membrane radius. These effects lead to new and qualitatively different scaling of the filament’s drag with its length. This example highlights the key role of membrane geometry in protein transport and assembly.  

Bio: Ehssan Nazockdast received his B.S. and M.S. degrees in polymer engineering from Amirkabir University in 2004 and 2007, respectively. He received his Ph.D. in chemical engineering from City College of New York in 2013. He did his postdoctoral studies at Courant Institute of Mathematical Sciences and spent another year as a postdoctoral researcher at Flatiron Institute (Simons Foundation). Ehssan joined the University of North Carolina at Chapel Hill in 2017, as an assistant professor, where he is currently working.     

Research in Nazockdast’s group broadly involves using physical modeling and simulations to study the dynamical behavior of soft and active biological materials. He is a recipient of NSF Career award in 2019. 

Host: Ali Mohraz