Small-Angle X-ray Scattering Studies on the Structure of Disc-Shaped Bicelles Incorporated with Neutral PEGylated Lipids

Abstract

In this study, small-angle X-ray scattering (SAXS) is successfully employed to investigate the structure of the DPPC/diC7PC disc-shaped bicelles incorporated with different amounts of C16-PEG2000-Ceramide lipids. The incorporation of the C16-PEG2000-Ceramide lipids could provide an antifouling capability to the bicelle for biomedical applications. However, traditionally it is believed that most of the incorporated PEGlylated lipids should lie in the rim of the disc-shaped bicelle. In this study, high sensitivity SAXS reveals the distribution of the added C16-PEG2000-Ceramide lipids in both the planar region and in the rim of the bicelle. The PEG brushes of C16-PEG2000-Ceramide lipids form a second shell outside the lipid headgroup shell of the bicelle. A double shell disc bicelle model is used in analyzing the SAXS data. The lipid density of C16-PEG2000-Ceramide in the rim is found to be about 1.7 times the C16-PEG2000-Ceramide lipid density in the planar region for all three C16-PEG2000-Ceramide concentrations, 1, 2, and 3 mM. Moreover, the bicelle core radius can be predicted well using the actual molecular ratio of lipids in the planar region to the lipids in the rim of the bicelles in the model calculation.

Lipid Nanoparticle Technologies for Nucleic Acid Delivery: A Nanoarchitectonics Perspective

“…Due to the increased size of the headgroup in such cases, PEGylated lipids can assume a more cone‐like appearance than typical long‐chain phospholipids and may locate in the edge and/or planar regions of a bicelle disk. [ 197 ]…”

“…[ 203 ] While PEGylated lipids have a mainly cone‐like geometry, more detailed structural studies have shown that a neutral PEGylated lipid (C16‐PEG2000‐ceramide) can distribute across both the planar region and rims of bicellar disk. Of note, there is indeed an approximately, two‐fold greater density of PEGylated lipids in the rims, [ 197 ] however, it should also be noted that the broader distribution of the PEGylated lipid is advantageous for potential in vivo applications. In molecular dynamics simulations, it has also been shown that bicelles containing ligand‐modified PEGylated lipids are more easily internalized by cells than similarly functionalized liposomes due to more favorable membrane energetics [ 204 ] (see also other examples of bicelles with improved cellular uptake properties over liposomes [ 205 ] ).…”

“…Due to the increased size of the headgroup in such cases, PEGylated lipids can assume a more cone-like appearance than typical long-chain phospholipids and may locate in the edge and/or planar regions of a bicelle disk. [197] There are also a few practical points to highlight: 1) the q-ratio must be within a certain range to form bicelle disks while other morphologies can form in different q-ratio ranges; [198] 2) the planar region of bicelle disks can present a membrane-mimicking environment, especially in cases where biologically relevant phospholipids are used. In certain cases, phospholipids and cholesterol can both be incorporated in the planar region and can form phase-separated domains in some cases; [199] 3) bicelle preparation should take place at a sufficiently high temperature so that all lipid components, especially the long-chain phospholipids, in the mixture are in the fluid phase.…”

Dynamic Behavior of the Structural Phase Transition of Hydrogel Formation Induced by Temperature Ramp and Addition of Ibuprofen

“…21 In some lipid systems, for instance, the assembly structures are important to the study of the interaction of membranes and assist the simulating membrane template for accommodating membrane proteins. 22,23 Even some in vitro drug release and diffusion experiments have shown that the drug release rate is faster in the cubic phase than in the hexagonal phase. 1,24 Inside the reverse cubic structure, water channels are continuous but nonintersecting.…”

“…Different micelle packings establish different delivery paths for the drugs and even the drug encapsulation capability, which is significantly related to the performance of drug release . In some lipid systems, for instance, the assembly structures are important to the study of the interaction of membranes and assist the simulating membrane template for accommodating membrane proteins. , Even some in vitro drug release and diffusion experiments have shown that the drug release rate is faster in the cubic phase than in the hexagonal phase. , Inside the reverse cubic structure, water channels are continuous but nonintersecting . However, water channels in the reversed hexagonal phase are smaller in diameter and close to each other with a large interfacial curvature .…”