Site-specific DNA-controlled fusion of single lipid vesicles to supported lipid bilayers.

We investigate the Ca(2+)-triggered fusion of lipid vesicles site-selectively tethered to a DNA-modified supported lipid bilayer array, with the DNA strands designed such that hybridization occurs in a zipperlike fashion. Prior to the addition of Ca(2+), which is observed to induce docking and subsequent fusion (within 200 ms), the vesicles display lateral mobility determined by the number of tethers. Fusion is observed to require around ten DNA strands per vesicle, but does not occur at higher DNA coverage. However, despite the fact that fusion was restricted to occurring for vesicles tethered with around ten DNA strands, there is no correlation between single-vesicle diffusivity and fusogenicity. A possible scenario for the DNA-induced fusion machinery, consistent with these observations, is that prior to Ca(2+)-induced docking, the vesicles diffuse with a small number (2-4) of DNA tethers. Upon addition of Ca(2+), the vesicles dock, presumably due to bridging of lipid head groups. Fusion then occurs under conditions where 10-16 DNA tethers form and rearrange at the rim of the contact region between a docked vesicle and the SLB. The time required for this rearrangement, which may include both DNA hybridization and dehybridization during zipping, is expected to represent the observed docking and fusion time of less than 200 ms.

[1]  J. Vörös,et al.  G‐protein coupled receptor array technologies: Site directed immobilisation of liposomes containing the H1‐histamine or M2‐muscarinic receptors , 2009, Proteomics.

[2]  Hana Robson Marsden,et al.  A reduced SNARE model for membrane fusion. , 2009, Angewandte Chemie.

[3]  Hiroaki Suzuki,et al.  Ninety-six-well planar lipid bilayer chip for ion channel recording Fabricated by hybrid stereolithography , 2009, Biomedical microdevices.

[4]  Fredrik Höök,et al.  A method improving the accuracy of fluorescence recovery after photobleaching analysis. , 2008, Biophysical journal.

[5]  F. Höök,et al.  Determinants for membrane fusion induced by cholesterol-modified DNA zippers. , 2008, The journal of physical chemistry. B.

[6]  Hywel Morgan,et al.  Controlled delivery of proteins into bilayer lipid membranes on chip. , 2007, Lab on a chip.

[7]  Raphael Zahn,et al.  DNA-induced programmable fusion of phospholipid vesicles. , 2007, Journal of the American Chemical Society.

[8]  S. Boxer,et al.  Diffusive dynamics of vesicles tethered to a fluid supported bilayer by single-particle tracking. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[9]  B. L. de Groot,et al.  Sequential N‐ to C‐terminal SNARE complex assembly drives priming and fusion of secretory vesicles , 2006, The EMBO journal.

[10]  Edwin R Chapman,et al.  SNARE-driven, 25-millisecond vesicle fusion in vitro. , 2005, Biophysical journal.

[11]  J. Benkoski,et al.  Lateral mobility of tethered vesicle-DNA assemblies. , 2005, The journal of physical chemistry. B.

[12]  Fan Zhang,et al.  Hemifusion in SNARE-mediated membrane fusion , 2005, Nature Structural &Molecular Biology.

[13]  Horst Vogel,et al.  Investigating cellular signaling reactions in single attoliter vesicles. , 2005, Journal of the American Chemical Society.

[14]  A. Brunger,et al.  Single molecule observation of liposome-bilayer fusion thermally induced by soluble N-ethyl maleimide sensitive-factor attachment protein receptors (SNAREs). , 2004, Biophysical journal.

[15]  T. Söllner Intracellular and viral membrane fusion: a uniting mechanism. , 2004, Current opinion in cell biology.

[16]  J. Rothman,et al.  Imaging single membrane fusion events mediated by SNARE proteins. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Fredrik Höök,et al.  Characterization of DNA immobilization and subsequent hybridization on a 2D arrangement of streptavidin on a biotin-modified lipid bilayer supported on SiO2. , 2003, Analytical chemistry.

[18]  S. Boxer,et al.  Arrays of mobile tethered vesicles on supported lipid bilayers. , 2003, Journal of the American Chemical Society.

[19]  T. McIntosh,et al.  Influence of lipid composition on physical properties and peg-mediated fusion of curved and uncurved model membrane vesicles: "nature's own" fusogenic lipid bilayer. , 2001, Biochemistry.

[20]  Benedikt Westermann,et al.  SNAREpins: Minimal Machinery for Membrane Fusion , 1998, Cell.

[21]  B. Lentz,et al.  Evolution of lipidic structures during model membrane fusion and the relation of this process to cell membrane fusion. , 1997, Biochemistry.

[22]  M. Saxton Single-particle tracking: the distribution of diffusion coefficients. , 1997, Biophysical journal.

[23]  B. Lentz,et al.  Binding of bovine factor Va to phosphatidylcholine membranes. , 1996, Biophysical journal.

[24]  K. Jacobson,et al.  Lateral diffusion of lipids and proteins in bilayer membranes , 1984 .

[25]  C. Altenbach,et al.  Ca2+ binding to phosphatidylcholine bilayers as studied by deuterium magnetic resonance. Evidence for the formation of a Ca2+ complex with two phospholipid molecules. , 1984, Biochemistry.

[26]  D. Papahadjopoulos,et al.  Studies on the mechanism of membrane fusion: kinetics of calcium ion induced fusion of phosphatidylserine vesicles followed by a new assay for mixing of aqueous vesicle contents. , 1980, Biochemistry.

[27]  J. Zimmerberg,et al.  Fusion of phospholipid vesicles with planar phospholipid bilayer membranes. II. Incorporation of a vesicular membrane marker into the planar membrane , 1980, The Journal of general physiology.