Conformational Dynamics of Dry Lamellar Crystals of Sugar Based Lipids: An Atomistic Simulation Study

Abstract

The rational design of a glycolipid application (e.g. drug delivery) with a tailored property depends on the detailed understanding of its structure and dynamics. Because of the complexity of sugar stereochemistry, we have undertaken a simulation study on the conformational dynamics of a set of synthetic glycosides with different sugar groups and chain design, namely dodecyl β-maltoside, dodecyl β-cellobioside, dodecyl β-isomaltoside and a C12C10 branched β-maltoside under anhydrous conditions. We examined the chain structure in detail, including the chain packing, gauche/trans conformations and chain tilting. In addition, we also investigated the rotational dynamics of the headgroup and alkyl chains. Monoalkylated glycosides possess a small amount of gauche conformers (∼20%) in the hydrophobic region of the lamellar crystal (LC) phase. In contrast, the branched chain glycolipid in the fluid Lα phase has a high gauche population of up to ∼40%. Rotational diffusion analysis reveals that the carbons closest to the headgroup have the highest correlation times. Furthermore, its value depends on sugar type, where the rotational dynamics of an isomaltose was found to be 11–15% and more restrained near the sugar, possibly due to the chain disorder and partial inter-digitation compared to the other monoalkylated lipids. Intriguingly, the present simulation demonstrates the chain from the branched glycolipid bilayer has the ability to enter into the hydrophilic region. This interesting feature of the anhydrous glycolipid bilayer simulation appears to arise from a combination of lipid crowding and the amphoteric nature of the sugar headgroups.

Synthesis, Simulation, and Self-Assembly of a Model Amphiphile To Push the Limits of Block Polymer Nanopatterning

“…There have been several experimental studies involving glycolipids that can adopt similar lamellar phases, − but most rely on synthesizing small libraries of molecules to uncover the desired nanostructures. Moreover, molecular simulations are rare for these systems and usually focus on understanding and rationalizing experimental results . Here we describe a computational prediction of an amphiphilic molecule that could achieve the desired small spacings and the subsequent preparation of a bespoke sample to verify the prediction.…”

Detecting local heterogeneity and ionization ability in the head group region of different lipidic phases using modified fluorescent probes

“…Figure 4 shows the possible locations of the HBO probes. The association of the sugar group with the lipophilic moiety is made possible by the sugar amphoteric nature via the saccharide hydrophobic face 52 53 , thus stabilizing the mostly hydrophobic backbone of HBO. In a related study, Loura and Ramalho reported that when labelling 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) bilayers with 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) acyl-chain as a fluorescent probe, the NBD fluorophore adopts a transverse location closer to the water/lipid interface than to the center of the bilayer 54 .…”

Phase sensitive molecular dynamics of self-assembly glycolipid thin films: A dielectric spectroscopy investigation

“…16 Therefore, dynamic investigation of the anhydrous systems is timely to support the growing scientific interest in the thermotropic lipidic phases from the seminal work of Jeffrey 17 and more recently those of Ericsson et al 18 and Auvray et al 19 Considering these points, we have concentrated our efforts on studying the thermotropic glycolipid phases in the absence of a solvent. 20,21 In addition, we have also previously reported on the pyroelectric behavior in dry glycolipids. 22 In the ensuing study here, we have investigated the dielectric properties of Guerbet maltosides to establish the diffusion mechanism and the dynamic of the materials without the solvent effect.…”