Columnar DNA Superlattices in Lamellar <i>o</i>-Ethylphosphatidylcholine Lipoplexes:  Mechanism of the Gel-Liquid Crystalline Lipid Phase Transition

Koynova, Rumiana; MacDonald, Robert C.

doi:10.1021/nl049191k

Cited by 36 publications

(56 citation statements)

References 23 publications

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“…The lamellar repeat distance of 4.73 nm is higher than that of the symmetric chain ethyldistearoylphosphatidylcholine in its gel phase (d ϭ 4.3 nm) (23). Because it has been established that the saturated symmetric chain EPCs form a fully interdigitated gel phase (3,23,25), this difference indicates that the gel phase of the asymmetric chain C18:0͞C10-EPC is of the partially interdigitated variety (24). The lamellar arrangement is preserved in the hydrated C18:0͞C10-EPC when heating to 90°C.…”

Section: Structure and Phase Behavior Of Cationic Lipid Aggregates Andmentioning

confidence: 76%

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An intracellular lamellar–nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents

Koynova

Wang

MacDonald

2006

Proc. Natl. Acad. Sci. U.S.A.

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149

163

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Two cationic phospholipid derivatives with asymmetric hydrocarbon chains were synthesized: ethyl esters of oleoyldecanoylethylphosphatidylcholine (C18:1͞C10-EPC) and stearoyldecanoylethylphosphatidylcholine (C18:0͞C10-EPC). The former was 50 times more effective as a DNA transfection agent (human umbilical artery endothelial cells) than the latter, despite their similar chemical structure and virtually identical lipoplex organization. A likely reason for the superior effectiveness of C18:1͞C10-EPC relative to C18:0͞C10-EPC (and to many other cationic lipoids) was suggested by the phases that evolved when these lipoids were mixed with negatively charged membrane lipid formulations. The saturated C18:0͞C10-EPC remained lamellar in mixtures with biomembranemimicking lipid formulations [e.g., dioleoyl-phosphatidylcholine͞ dioleoyl-phosphatidylethanolamine͞dioleoyl-phosphatidylserine͞ cholesterol at 45:20:20:15 (wt͞wt)]; in contrast, the unsaturated C18:1͞C10-EPC exhibited a lamellar-nonlamellar phase transition in such mixtures, which took place at physiological temperatures, Ϸ37°C. As is well known, lipid vehicles exhibit maximum leakiness and contents release in the vicinity of phase transitions, especially those involving nonlamellar phase formation. Moreover, nonlamellar phase-forming compositions are frequently highly fusogenic. Indeed, FRET experiments showed that C18:1͞C10-EPC exhibits lipid mixing with negatively charged membranes that is several times more extensive than that of C18:0͞C10-EPC. Thus, C18:1͞C10-EPC lipoplexes are likely to easily fuse with membranes, and, as a result of lipid mixing, the resultant aggregates should exhibit extensive phase coexistence and heterogeneity, thereby facilitating DNA release and leading to superior transfection efficiency. These results highlight the phase properties of the carrier lipid͞cellular lipid mixtures as a decisive factor for transfection success and suggest a strategy for the rational design of superior cationic lipid carriers.lipofection ͉ lipoplex ͉ mesophase I mportant therapeutic procedures, such as gene transfection and gene silencing, require efficient delivery of genetic material to cells. Synthetic cationic lipoids, which form complexes (lipoplexes) with polyanionic DNA, are promising gene carriers (1). Understanding the mechanism of lipid-mediated DNA delivery (lipofection) is essential for the successful application and rational design and synthesis of novel cationic lipoid compounds for enhanced gene delivery. Although considerable improvement in the transfection properties of cationic lipoids has come from the synthesis of new kinds of cationic amphiphiles or from the inclusion of noncationic helper lipids, an effective alternative strategy was recently described: The combination of two cationic lipid derivatives having the same headgroup but different hydrocarbon chains can synergistically enhance transfection (2). For example, the optimal combination of the long chain͞medium chain lipoids, dioleoyl-and dilauroyl-ethylphosphatidylcholines, de...

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Section: Structure and Phase Behavior Of Cationic Lipid Aggregates Andmentioning

confidence: 76%

“…2A) slightly lower than that of the ethylphosphatidylcholine (EPC) with saturated symmetric chain ethyldistearoylphosphatidylcholine (diC18:0-EPC) (23). When C18:0͞C10-EPC cools, it undergoes a phase transition to another lamellar phase with a smaller repeat distance (d ϭ 4.73 nm).…”

Section: Structure and Phase Behavior Of Cationic Lipid Aggregates Andmentioning

confidence: 96%

An intracellular lamellar–nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents

Koynova

Wang

MacDonald

2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

149

163

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“…This may help explain why lipoplexes made from cationic o-ethylphosphatidylcholines with disaturated hydrocarbon chains are effective transfection agents [98,99]. The structure and transfection capability of cationic phospholipid-DNA complexes are dependent on preparation conditions and ionic strength [98,100].…”

Section: The Interdigitated Gel Phase In Cationic Lipidsmentioning

confidence: 99%

“…In some instances, DNA can be sandwiched between interdigitated gel phase lipid sheets into a rectangular columnar two-dimensional superlattice [97,99]. The gel-to-liquid crystalline phase transition results in the contraction of the DNA strand arrays so that the mean charge density is balanced with the increased positive charge of the non-interdigitated lipid.…”

Section: The Interdigitated Gel Phase In Cationic Lipidsmentioning

confidence: 99%

“…The gel-to-liquid crystalline phase transition results in the contraction of the DNA strand arrays so that the mean charge density is balanced with the increased positive charge of the non-interdigitated lipid. Additionally, in the non-interdigitated liquid crystalline phase, the interlamellar correlation in DNA ordering is no longer observed [99].…”

Section: The Interdigitated Gel Phase In Cationic Lipidsmentioning

confidence: 99%

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Differential Scanning Calorimetry Studies of Phospholipid Membranes: The Interdigitated Gel Phase

Smith¹,

Dea²

2013

Applications of Calorimetry in a Wide Context - Differential Scanning Calorimetry, Isothermal Titration Calorimetry and Microca

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Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

et al. 2019

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Amphiphilic lipids aggregate in aqueous solution into a variety of structural arrangements. Among the plethora of ordered structures that have been reported, many have also been observed in nature. In addition, due to their unique morphologies, the hydrophilic and hydrophobic domains, very high internal interfacial surface area, and the multitude of possible order−order transitions depending on environmental changes, very promising applications have been developed for these systems in recent years. These include crystallization in inverse bicontinuous cubic phases for membrane protein structure determination, generation of advanced materials, sustained release of bioactive molecules, and control of chemical reactions. The outstanding diverse functionalities of lyotropic liquid crystalline phases found in nature and industry are closely related to the topology, including how their nanoscopic domains are organized. This leads to notable examples of correlation between structure and macroscopic properties, which is itself central to the performance of materials in general. The physical origin of the formation of the known classes of lipidic lyotropic liquid crystalline phases, their structure, and their occurrence in nature are described, and their application in materials science and engineering, biology, medical, and pharmaceutical products, and food science and technology are exemplified. Amphiphilic LipidsThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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Columnar DNA Superlattices in Lamellar o-Ethylphosphatidylcholine Lipoplexes: Mechanism of the Gel-Liquid Crystalline Lipid Phase Transition

Cited by 36 publications

References 23 publications

An intracellular lamellar–nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents

An intracellular lamellar–nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents

Differential Scanning Calorimetry Studies of Phospholipid Membranes: The Interdigitated Gel Phase

Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

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