Direct visualization of dispersed lipid bicontinuous cubic phases by cryo-electron tomography

Abstract

Bulk and dispersed cubic liquid crystalline phases (cubosomes), present in the body and in living cell membranes, are believed to play an essential role in biological phenomena. Moreover, their biocompatibility is attractive for nutrient or drug delivery system applications. Here the three-dimensional organization of dispersed cubic lipid self-assembled phases is fully revealed by cryo-electron tomography and compared with simulated structures. It is demonstrated that the interior is constituted of a perfect bicontinuous cubic phase, while the outside shows interlamellar attachments, which represent a transition state between the liquid crystalline interior phase and the outside vesicular structure. Therefore, compositional gradients within cubosomes are inferred, with a lipid bilayer separating at least one water channel set from the external aqueous phase. This is crucial to understand and enhance controlled release of target molecules and calls for a revision of postulated transport mechanisms from cubosomes to the aqueous phase.

Dynamics of different steps of the photopyrolytic cycle of an eminent anticancer drug topotecan inside biocompatible lyotropic liquid crystalline systems

“…5 ) and tri-fold (120 ) connectivity respectively (Scheme 1). 10,32 The water channel in both cubic phases is unconnected, which is recently also visualized by Cryo-Electron Tomography (CET) technique.…”

“…[1][2][3][4][5][6][7] Lipid based 'so' and 'wet' lyotropic liquid crystalline (LLC) materials are recognized as the 'smart materials' owing to their remarkable topology, [8][9][10] stimuli responsive phase change 11,12 and multitude of applications in the biological, 5,13 materials 1-7 and pharmaceutical 14,15 elds. These materials can be synthesized by the binary mixture of an amphiphilic surfactant (especially lipid) and water.…”

“…Moreover, in Ia3d phase the two water channels are not identical to each other, but they are enantiomeric in nature. 10,32 However, in Pn3m phase two autonomous water network are separated by the continuous layer of lipid molecules with four way junctions at the tetrahedral (109. 5 ) angle (Scheme 1), and in this phase both water channels are identical in nature.…”

“…10,32 Thus, from the architecture of different LLC phases, it is clear that H II phase provides most restricted pathway during 'Grotthuss' proton diffusion process owing to its cylindrical topology (Scheme 1). Interestingly, Pn3m phase can provide the faster pathway for proton diffusion due to tetra fold (109.…”

A macroscopic H + and Cl − ions pump via reconstitution of EcClC membrane proteins in lipidic cubic mesophases

“…The latter two symmetries are of particular significance in fundamental and applied sciences because they coexist at thermodynamic equilibrium with excess water (1,4), involving an immediate plethora of direct implications. For example, bicontinuous lipidic cubic phases are now recognized as a powerful tool for drug delivery (5,6) and as efficient vectors for siRNA and DNA transfection (7,8) and have been observed in numerous biological systems, where they seem to have an apparent relation to pathological states of the cell (9).…”