Mobility in geometrically confined membranes

Abstract

Lipid and protein lateral mobility is essential for biological function. Our theoretical understanding of this mobility can be traced to the seminal work of Saffman and Delbrück, who predicted a logarithmic dependence of the protein diffusion coefficient (i) on the inverse of the size of the protein and (ii) on the "membrane size" for membranes of finite size [Saffman P, Delbrück M (1975) Proc Natl Acad Sci USA 72:3111-3113]. Although the experimental proof of the first prediction is a matter of debate, the second has not previously been thought to be experimentally accessible. Here, we construct just such a geometrically confined membrane by forming lipid bilayer nanotubes of controlled radii connected to giant liposomes. We followed the diffusion of individual molecules in the tubular membrane using single particle tracking of quantum dots coupled to lipids or voltage-gated potassium channels KvAP, while changing the membrane tube radius from approximately 250 to 10 nm. We found that both lipid and protein diffusion was slower in tubular membranes with smaller radii. The protein diffusion coefficient decreased as much as 5-fold compared to diffusion on the effectively flat membrane of the giant liposomes. Both lipid and protein diffusion data are consistent with the predictions of a hydrodynamic theory that extends the work of Saffman and Delbrück to cylindrical geometries. This study therefore provides strong experimental support for the ubiquitous Saffman-Delbrück theory and elucidates the role of membrane geometry and size in regulating lateral diffusion.

Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes

“…The mobility of DiI decreased as the molecules approached the tips of filopodia or spines (Fig. 3E), possibly due to the higher local membrane curvature (36) and the different composition of membrane proteins at these locations.…”

BIN1/M-Amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin

“…27). It is thus likely that curvature will amplify this effect, as curvature significantly reduces protein diffusion 28 and also affects lipids dynamics 26 . Under such conditions, one would expect that the transient segregation of PtdIns(4,5)P 2 generates a positive feedback, allowing proteins that selectively interact with PtdIns(4,5)P 2 to locally accumulate on PtdIns(4,5)P 2 -enriched areas, independently of their ability to polymerize (that is, AP180 and Epsin2).…”

Strong influence of periodic boundary conditions on lateral diffusion in lipid bilayer membranes

“…Experimental measurements of L sd for lipid bilayer systems are typically in the 100 nm to micron range. 24,25,[38][39][40][41][42] In coarse-grained models, some details of lipid and solvent structure are lost and there is no reason to expect close correspondence to experimental numbers. For example, in the coarse-grained MARTINI force field, 5 η m has been determined to be 1.2 × 10 −8 P cm for DPPC bilayers, with water viscosity η f = 7 × 10 −3 P. 9 Within MARTINI simulations, we expect L sd ≈ 8.6 nm-much smaller than the experimental range.…”