Membrane Shape Modulates Transmembrane Protein Distribution

Abstract

Summary Although membrane shape varies greatly throughout the cell, the contribution of membrane curvature to transmembrane protein targeting is unknown due to the numerous sorting mechanisms taking place concurrently in cells. To isolate the effect of membrane shape, cellsized Giant Unilamellar Vesicles (GUVs) containing either the potassium channel, KvAP, or water channel, AQP0, were used to form membrane nanotubes with controlled radii. While the AQP0 concentrations in flat and curved membranes were indistinguishable, KvAP was enriched in the tubes, with greater enrichment in more highly curved membranes. FRAP measurements showed that both proteins could freely diffuse through the neck between the tube and GUV, and the effect of each protein on membrane shape and stiffness was characterized using a thermodynamic sorting model. This study establishes the importance of membrane shape for targeting transmembrane proteins, and provides a method for determining the effective shape and flexibility of membrane proteins.

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

“…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

“…Here, we call these objects that induce isotropic spontaneous curvature an isotropic inclusion. Their assembly into preferred curvature regions [23][24][25][26][27] and membrane-mediated interactions between the colloids [28][29][30] have been previously explored.…”

Curvature correction to the mobility of fluid membrane inclusions

“…Such fluctuations have an effect on the membrane as well as the inclusion shape. Indeed, unlike [5,10], we find above that by taking into account thermal fluctuations we are also able to accurately capture the membrane tension dependent mobility of an AQP0 inclusion even when its average contact angle ( β ∼ β 0 ) vanishes (β 0 ∼ 0) [22]. Furthermore, using our theory we can now be seen to be able to directly probe and investigate inclusion elasticity (governed by the elastic constant k p ) via measurements of the inclusion's mobility.…”

“…In [5] it was found that the diffusion constant for a voltage-gated potassium channel (KvAP) protein was significantly increased, as the surface tension was increased, whereas the mobility of a water channel aquaporin 0 (AQP0) protein was, relatively, fairly insensitive to membrane tension. This is thought to occur due to the fact that KvAP locally bends the membrane considerably, forming an effectively conical inclusion, whereas AQP0 is thought to negligibly deform the bilayer locally [5,22]. Shown in fig.…”