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Determinants for Membrane Fusion Induced by Cholesterol-Modified DNA Zippers.

Stengel, Gudrun LU ; Simonsson, Lisa LU ; Campbell, Richard LU and Höök, Fredrik LU (2008) In The Journal of Physical Chemistry Part B 112(28). p.8264-8274
Abstract
Intracellular membrane fusion is coordinated by membrane-anchored fusion proteins. The cytosolic domains of these proteins form a specific complex that pulls the membranes into close proximity. Although some results indicate that membrane merger can be accomplished solely on the basis of proximity, others emphasize the importance of bilayer stress exerted by transmembrane peptides. In a reductionist approach, we recently introduced a fusion machinery built from cholesterol-modified DNA zippers to mimic fusion protein function. Aiming to further optimize DNA-mediated fusion, we varied in this work length and number of DNA strands and used either one or two cholesterol groups for membrane anchoring of DNA. The results reveal that the use of... (More)
Intracellular membrane fusion is coordinated by membrane-anchored fusion proteins. The cytosolic domains of these proteins form a specific complex that pulls the membranes into close proximity. Although some results indicate that membrane merger can be accomplished solely on the basis of proximity, others emphasize the importance of bilayer stress exerted by transmembrane peptides. In a reductionist approach, we recently introduced a fusion machinery built from cholesterol-modified DNA zippers to mimic fusion protein function. Aiming to further optimize DNA-mediated fusion, we varied in this work length and number of DNA strands and used either one or two cholesterol groups for membrane anchoring of DNA. The results reveal that the use of two cholesterol anchors is essential to prevent cDNA strands from shuttling to the same membrane, which leads to vesicle release instead of membrane merger. A surface coverage of 6-13 DNA strands was a precondition for efficient fusion, whereas fusion was insensitive to DNA length within the tested range. Besides lipid mixing, we also demonstrate DNA-induced content mixing of large unilamellar vesicles composed of the most abundant cellular lipids phosphatidylcholine, phosphatidylethanolamine, cholesterol, and sphingomyelin. Taken together, DNA-mediated fusion emerges as a promising tool for the functionalization of artificial and biological membranes and may help to dissect the functional role of fusion proteins. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
112
issue
28
pages
8264 - 8274
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000257542500008
  • pmid:18570399
  • scopus:50249174449
ISSN
1520-5207
DOI
10.1021/jp802005b
language
English
LU publication?
yes
id
189d8ba8-3250-4ba7-9458-792e53f1d03f (old id 1168582)
date added to LUP
2016-04-01 14:00:03
date last changed
2022-02-19 08:36:13
@article{189d8ba8-3250-4ba7-9458-792e53f1d03f,
  abstract     = {{Intracellular membrane fusion is coordinated by membrane-anchored fusion proteins. The cytosolic domains of these proteins form a specific complex that pulls the membranes into close proximity. Although some results indicate that membrane merger can be accomplished solely on the basis of proximity, others emphasize the importance of bilayer stress exerted by transmembrane peptides. In a reductionist approach, we recently introduced a fusion machinery built from cholesterol-modified DNA zippers to mimic fusion protein function. Aiming to further optimize DNA-mediated fusion, we varied in this work length and number of DNA strands and used either one or two cholesterol groups for membrane anchoring of DNA. The results reveal that the use of two cholesterol anchors is essential to prevent cDNA strands from shuttling to the same membrane, which leads to vesicle release instead of membrane merger. A surface coverage of 6-13 DNA strands was a precondition for efficient fusion, whereas fusion was insensitive to DNA length within the tested range. Besides lipid mixing, we also demonstrate DNA-induced content mixing of large unilamellar vesicles composed of the most abundant cellular lipids phosphatidylcholine, phosphatidylethanolamine, cholesterol, and sphingomyelin. Taken together, DNA-mediated fusion emerges as a promising tool for the functionalization of artificial and biological membranes and may help to dissect the functional role of fusion proteins.}},
  author       = {{Stengel, Gudrun and Simonsson, Lisa and Campbell, Richard and Höök, Fredrik}},
  issn         = {{1520-5207}},
  language     = {{eng}},
  number       = {{28}},
  pages        = {{8264--8274}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{The Journal of Physical Chemistry Part B}},
  title        = {{Determinants for Membrane Fusion Induced by Cholesterol-Modified DNA Zippers.}},
  url          = {{http://dx.doi.org/10.1021/jp802005b}},
  doi          = {{10.1021/jp802005b}},
  volume       = {{112}},
  year         = {{2008}},
}