Lipid doping of the sponge (L3) mesophase

Christopher Brasnett, Adam Squires, Andrew J. Smith, Annela M. Seddon

Research output: Contribution to journalArticlepeer-review


The polymorphism of lipid aggregates has long attracted detailed study due to the myriad factors that determine the final mesophase observed. This study is driven by the need to understand mesophase behaviour for a number of applications, such as drug delivery and membrane protein crystallography. In the case of the latter, the role of the so-called ‘sponge’ (L3) mesophase has been often noted, but not extensively studied by itself. The L3 mesophase can be formed in monoolein/water systems on the addition of butanediol to water, which partitions the headgroup region of the membrane, and decreases its elastic moduli. Like cubic mesophases, it is bicontinuous, but unlike them, has no long-range translational symmetry. In our present study, we show that the formation of the L3 phase can delicately depend on the addition of dopant lipids to the mesophase. While electrostatically neutral molecules similar in shape to monoolein (DOPE, cholesterol) have little effect on the general mesophase behaviour, others (DOPC, DDM) significantly reduce the composition at which it can form. Additionally, we show that by combining cholesterol with the anionic lipid DOPG, it is possible to form the largest stable L3 mesophases observed to date, with characteristic lengths over 220 Å.
Original languageEnglish
Pages (from-to)6569-6577
JournalSoft Matter
Issue number34
Early online date14 Aug 2023
Publication statusE-pub ahead of print - 14 Aug 2023

Bibliographical note

The Ganesha X-ray scattering apparatus used for this research was purchased under EPSRC Grant ‘Atoms to Applications’ Grant ref. EP/K035746/1. CB acknowledges studentship funding from EPSRC EP/N509619/1. We are grateful to Diamond Light Source for beam time awards (SM17767-1 and SM29558-1) to this project and to the staff, particularly Nick Terrill and Sam Burholt, on beamlines I22 and DL-SAXS for their support.


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