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Influence of preparation path on the formation of discs and threadlike micelles in DSPE-PEG(2000)/lipid systems
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
2008 (English)In: Biophysical Chemistry, ISSN 0301-4622, E-ISSN 1873-4200, Vol. 132, no 2-3, 97-103 p.Article in journal (Refereed) Published
Abstract [en]

In a recent study we showed that the surfactant 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[methoxy(polyethy lene glycol)-2000 (DSPE-PEG(2000)) induce mixed micelles of either threadlike or discoidal shape when mixed with different types of lipids. In certain lipid systems the discoidal micelles adapt sizes large enough to be characterized as bilayer discs. The discs hold great potential for use in various biotechnical applications and may e.g. be used as model membranes in drug/membrane partition studies. Depending on the application, discs with certain characteristics, such as a particular size or size homogeneity, may be required. These factors can in our experience be influenced by the preparation method. In this study we systematically investigated three different PEG-lipid/lipid mixtures prepared by four commonly used preparation techniques. The techniques used were simple hydration, freeze-thawing, sonication and detergent depletion, and the aggregate size and structure was analyzed by cryo transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS). Our results show that the type and size of the micellar structure found, as well as the structure homogeneity of the preparation, can be modified by the choice of preparation path.

Place, publisher, year, edition, pages
2008. Vol. 132, no 2-3, 97-103 p.
Keyword [en]
bilayer disc, phospholipids, PEG-lipid, cryo-TEM
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96191DOI: 10.1016/j.bpc.2007.10.011ISI: 000252487800004PubMedID: 18006210OAI: oai:DiVA.org:uu-96191DiVA: diva2:170681
Available from: 2007-09-14 Created: 2007-09-14 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Bilayer Discs - Fundamental Investigations and Applications of Nanosized Membrane Models
Open this publication in new window or tab >>Bilayer Discs - Fundamental Investigations and Applications of Nanosized Membrane Models
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The bilayer disc is a flat, lipid aggregate structure in the nanometre regime. It is composed of a bilayer of amphiphilic molecules with micelle-forming amphiphilic molecules supporting the rim, which prevent disc fusion and self-closure. Stable discs have been found in lipid mixtures containing polyethylene glycol (PEG)-lipids as a rim-stabilizing component. One of the aims of the work described in this thesis was to increase the fundamental knowledge and understanding of the systems in which these discs are formed. Other micelle-forming surfactants apart from PEG-lipids were also explored to see if they could be used to stabilize the disc aggregate structure. Due to the similarities of these lipid discs with natural membranes it was hypothesized that they could be used as models for biological membranes.

It was demonstrated that discs are formed in PEG-lipid/lipid systems when the lipid mixture contains components that reduce the spontaneous curvature and increase the monolayer bending rigidity. Discoidal structures are furthermore preferred when the lipids are in the gel phase, probably due to a combination of high bending rigidity and reduced PEG-lipid/lipid miscibility. The disc size could be varied by changing the PEG-lipid concentration. The size and size homogeneity of the discs could also be varied by changing the preparation path. Generally, the preferences of certain lipid systems to form discs remained when the PEG-lipid was replaced by more conventional surfactants. However, discs prepared in PEG-lipid/lipid systems are more useful as model membranes because of their relatively large size and good temperature, dilution and long-term stability. Data obtained with isothermal titration calorimetry and drug partition chromatography indicate that these bilayer discs may serve as an attractive and sometimes superior alternative to liposomes in studies of drug-membrane interactions.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 340
Keyword
Chemistry, disc, threadlike micelle, liposome, model membrane, drug partitioning, cryo-TEM, Kemi
Identifiers
urn:nbn:se:uu:diva-8200 (URN)978-91-554-6962-7 (ISBN)
Public defence
2007-10-05, B22, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2007-09-14 Created: 2007-09-14 Last updated: 2010-03-04Bibliographically approved

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