title: Intermembrane docking reactions are regulated by membrane curvature.
abstract: The polymorphism of eukaryotic cellular membranes is a tightly regulated and well-conserved phenotype. Recent data have revealed important regulatory roles of membrane curvature on the spatio-temporal localization of proteins and in membrane fusion. Here we quantified the influence of membrane curvature on the efficiency of intermembrane docking reactions. Using fluorescence microscopy, we monitored the docking of single vesicle-vesicle pairs of different diameter (30-200 nm) and therefore curvature, as mediated by neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and streptavidin-biotin. Surprisingly, the intermembrane docking efficiency exhibited an ∼30-60 fold enhancement as a function of curvature. In comparison, synaptotagmin and calcium accelerate SNARE-mediated fusion in vitro by a factor of 2-10. To explain this finding, we formulated a biophysical model. On the basis of our findings, we propose that membrane curvature can regulate intermembrane tethering reactions and consequently any downstream process, including the fusion of vesicles and possibly viruses with their target membranes.
authors.affiliation: Bionanotechnology and Nanomedicine Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. akunding@me.com
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Kunding
authors.forename: Michael W
authors.initials: MW
authors.lastname: Mortensen
authors.forename: Sune M
authors.initials: SM
authors.lastname: Christensen
authors.forename: Vikram K
authors.initials: VK
authors.lastname: Bhatia
authors.forename: Ivan
authors.initials: I
authors.lastname: Makarov
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzler
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stamou
mesh_terms: D001360:Avidin / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008561:Membrane Fusion; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D050600:SNARE Proteins / Q000378:metabolism; D055672:Static Electricity; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D050600:SNARE Proteins; D053835:Unilamellar Liposomes; C093483:neutravidin; D001360:Avidin