IRSp53 senses negative membrane curvature and phase separates along membrane tubules

Abstract

BAR domain proteins contribute to membrane deformation in diverse cellular processes. The inverted-BAR (I-BAR) protein IRSp53, for instance, is found on the inner leaflet of the tubular membrane of filopodia; however its role in the formation of these structures is incompletely understood. Here we develop an original assay in which proteins are encapsulated in giant unilamellar vesicles connected to membrane nanotubes. Our results demonstrate that I-BAR dimers sense negative membrane curvature. Experiment and theory reveal that the I-BAR displays a non-monotonic sorting with curvature, and expands the tube at high imposed tension while constricting it at low tension. Strikingly, at low protein density and tension, protein-rich domains appear along the tube. This peculiar behaviour is due to the shallow intrinsic curvature of I-BAR dimers. It allows constriction of weakly curved membranes coupled to local protein enrichment at biologically relevant conditions. This might explain how IRSp53 contributes in vivo to the initiation of filopodia.

Onsager’s Variational Principle in Soft Matter: Introduction and Application to the Dynamics of Adsorption of Proteins onto Fluid Membranes

“…A constant membrane tension ensemble would require changes in membrane area and therefore lipid flows from a reservoir, which is at odds with a simple uniform dynamical model. Zhu et al (2012);Prévost et al (2015) have developed models that allow for exchange of lipids and proteins with a reservoir, albeit in equilibrium. We further assume that both the osmolarity and the hydraulic pressure are the same inside and outside of the tube.…”

“…On the chemical side, bilayers exhibit nonlinear chemical effects as a result of molecular crowding, such as nonlinear adsorption (Sorre et al, 2012) or nonlinear sorting of proteins between vesicles and tubules (Zhu et al, 2012;Aimon et al, 2014;Prévost et al, 2015). Thus, linearized chemo-mechanical models can only provide information about the onset of transitions (Shi and Baumgart, 2015), about dilute concentrations of protein on the surface (Góźdź, 2011), or about the response under very small perturbations (Callan-Jones et al, 2016).…”

Shape deformation of lipid membranes by banana-shaped protein rods: Comparison with isotropic inclusions and membrane rupture

“…Some of the BAR superfamily proteins, such as N-BAR proteins, also have hydrophobic insertions. Experimentally, the formation of membrane tubes and curvature-sensing by various types of BAR superfamily proteins have been observed [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Dysfunctional BAR proteins are considered to be implicated in neurodegenerative, cardiovascular, and neoplastic diseases.…”

Nanodomains in Biomembranes with Recycling

“…An efficient mechanism comes from the up-down symmetry breaking that a vast majority of proteins are supposed to impose to the membrane, leading to a local spontaneous membrane curvature [10]. The coupling between inclusion concentration and membrane curvature has recently received a striking experimental demonstration [27]. When grouped in a cluster, asymmetric proteins collectively shape the membrane and lead to spherical buds, the elastic energy of which grows faster than the number of proteins [28].…”

“…3, right) is given by Eq. [ 27 ]. With the reference parameter set, ν analytic 0.49, whereas the numerical solution gave νnum.…”