Abstract/Details

Small angle scatting studies of self assembly in lipid mixtures


2009 2009

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Abstract (summary)

Systems consisting of mixtures of a long and a short-tail lipid, commonly referred to as 'biclles', have recently shown promise in membrane protein crystallization and have been used for some time as an alignable media for use in NMR based protein structure determination. However, the phase behavior of these lipid mixtures remains poorly understood. This dissertation reports small angle scattering studies to gain an understanding of the structure and composition, as well as the mechanism of structural transformation by systematically tailoring those mixtures. A detailed understanding of the phase behavior is essential to adapting them for specific applications.

In DMPC/DHPC (or C14/C6) mixtures at temperatures ∼10-15°C below the melting transition temperature Tm of the long tail lipid C14, small angle neutron scattering (SANS) experiments with mixtures of hydrogenated and deuterated lipids give direct evidence of the segregated discoidal morphology, while use of standard mixed surfactant theories account to first order for the size of the discs. The deviation of their dilution induced growth from the fully segregated models, an evidence of net mixing of the long lipid into the short lipid rim, is confirmed by contrast enhanced SANS. Previously ignored and unaccounted for, such a mixing behavior is essential for the energetics of a self-assembled mixture of two lipids with vastly different spontaneous curvatures. When the low temperature study is extended to other phospholipid-detergent mixtures, universality of the discoidal phase is observed, highlighting the role of the rigid, gel state long lipid and the edge tension reducing properties of the short lipids in the self-assembly. As a step further, when the size of the smaller lipid species is increased to consist of eight carbon tails, (C14/C8 mixture), elongated tablet like aggregates with fiat, non circular cross-section are the predominant structures, as shown by complimentary SANS and SAXS (small angle X-ray scattering) techniques. Similar structures are also observed in C14/C6 mixtures at temperatures near and above the Tm of C14 lipids. Chain-melting at higher temperatures in C14/C6 mixtures and mixing of the two lipids due to decreasing chain length difference (or hydrophobic mismatch) in C14/C8 are found to be equivalent effects, affecting the interfacial and bulk properties of the aggregates, and leading to preferential growth in one-dimension.

Indexing (details)


Subject
Biophysics
Classification
0786: Biophysics
Identifier / keyword
Biological sciences; Lipid mixtures; Neutron scattering; Phospholipids; Self-assembly
Title
Small angle scatting studies of self assembly in lipid mixtures
Author
Singh, Divya
Number of pages
275
Publication year
2009
Degree date
2009
School code
0098
Source
DAI-B 69/12, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549939870
Advisor
Butler, Paul; Porcar, Lionel
University/institution
The Johns Hopkins University
University location
United States -- Maryland
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3340003
ProQuest document ID
304915826
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304915826
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