Steric Confinement of Proteins in Lipid Domains Can Drive Membrane Curvature and Tubulation

Abstract

Deformation of lipid membranes into curved structures such as buds and tubules is essential to many cellular processes. Lipid micro-domains are thought to co-localize with many curved membrane structures, inspiring ongoing exploration of a variety of roles for domains in membrane bending.We examined the role of lipid domains in spatial confinement of protein binding and discovered a new mechanism for curvature amplification that relies on global coupling. We formed giant unilamellar vesicles that contained insoluble lipid domains that strongly bound his-tagged proteins. We show that protein crowding on domain surfaces creates a protein layer that buckles outward, spontaneously bending the domain into stable, well-defined tubules as more proteins bind. In contrast to previously described bending mechanisms relying on local steric interactions between proteins and lipids (i.e. helix insertion into membranes), this mechanism produces tubules whose dimensions are defined by global parameters: binding energy and domain size. Our results suggest the intriguing possibility that domains can amplify membrane bending and define protrusion length scales by concentraing the steric interactions between the lipid bilayer and proteins. This mechanism may help explain the high curvatures induced by membrane bending proteins.View Large Image | View Hi-Res Image | Download PowerPoint Slide