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Title: The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range

Abstract

In this paper we investigate the pseudo-ternary phase diagram of glycerol monooleate (GMO), a cationic lipid (DOTAP - 1,2-dioleoyl-3-trimethylammonium propane), and a "PEGylated" lipid (DOPE-PEG - 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 kDa]) in excess water. We use small angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (Cryo-EM) to map out a phase diagram in a regime of low DOPE-PEG content (1–5 mol%), which is pertinent for the application of lipid systems as carriers of biomolecular cargo to cells. Pure GMO is known to self-assemble into bicontinuous cubic phases of the gyroid type at low water content and of the diamond type in excess water. These complex structures have numerous advantages reaching beyond drug delivery, e.g. as protein crystallization matrices but their formulation is challenging as very small contents of guest molecules can shift the phase behavior towards other geometries such as the lamellar phase. In this work we show that the ternary GMO/DOTAP/DOPE-PEG system allows the stabilization of bicontinuous cubic phases in excess water over a wide composition range. Furthermore, the symmetry of the phase can be tuned by varying the amount of PEGylated lipid, with the primitive type dominating at low DOPE-PEG content (1–3 mol%) and the diamond phase arising atmore » 5 mol% DOPE-PEG. In addition, we found that the diamond phase is virtually non-responsive to electrostatic swelling. In contrast, primitive bicontinuous cubic lattice dimensions swell up in equilibrium to 650 A with increased cationic lipid content.« less

Authors:
ORCiD logo [1]; ORCiD logo [1]
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  1. Univ. of Illinois at Urbana-Champaign, IL (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE Office of Science (SC)
OSTI Identifier:
1599450
Grant/Contract Number:  
1DP2EB024377–01; AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Soft Matter
Additional Journal Information:
Journal Volume: 15; Journal Issue: 6; Journal ID: ISSN 1744-683X
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE

Citation Formats

Leung, Sherry S. W., and Leal, Cecilia. The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range. United States: N. p., 2018. Web. doi:10.1039/C8SM02059K.
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Leung, Sherry S. W., & Leal, Cecilia. The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range. United States. https://doi.org/10.1039/C8SM02059K
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Leung, Sherry S. W., and Leal, Cecilia. Wed . "The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range". United States. https://doi.org/10.1039/C8SM02059K. https://www.osti.gov/servlets/purl/1599450.
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@article{osti_1599450,
title = {The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range},
author = {Leung, Sherry S. W. and Leal, Cecilia},
abstractNote = {In this paper we investigate the pseudo-ternary phase diagram of glycerol monooleate (GMO), a cationic lipid (DOTAP - 1,2-dioleoyl-3-trimethylammonium propane), and a "PEGylated" lipid (DOPE-PEG - 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 kDa]) in excess water. We use small angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (Cryo-EM) to map out a phase diagram in a regime of low DOPE-PEG content (1–5 mol%), which is pertinent for the application of lipid systems as carriers of biomolecular cargo to cells. Pure GMO is known to self-assemble into bicontinuous cubic phases of the gyroid type at low water content and of the diamond type in excess water. These complex structures have numerous advantages reaching beyond drug delivery, e.g. as protein crystallization matrices but their formulation is challenging as very small contents of guest molecules can shift the phase behavior towards other geometries such as the lamellar phase. In this work we show that the ternary GMO/DOTAP/DOPE-PEG system allows the stabilization of bicontinuous cubic phases in excess water over a wide composition range. Furthermore, the symmetry of the phase can be tuned by varying the amount of PEGylated lipid, with the primitive type dominating at low DOPE-PEG content (1–3 mol%) and the diamond phase arising at 5 mol% DOPE-PEG. In addition, we found that the diamond phase is virtually non-responsive to electrostatic swelling. In contrast, primitive bicontinuous cubic lattice dimensions swell up in equilibrium to 650 A with increased cationic lipid content.},
doi = {10.1039/C8SM02059K},
journal = {Soft Matter},
number = 6,
volume = 15,
place = {United States},
year = {Wed Nov 14 00:00:00 EST 2018},
month = {Wed Nov 14 00:00:00 EST 2018}
}
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https://doi.org/10.1039/C8SM02059K
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