Molecular dynamics simulations and NMR spectroscopy studies of trehalose–lipid bilayer systems

Abstract

The disaccharide trehalose (TRH) strongly affects the physical properties of lipid bilayers. We investigate interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH using NMR spectroscopy and molecular dynamics (MD) computer simulations. We compare dipolar couplings derived from DMPC/TRH trajectories with those determined (i) experimentally in TRH using conventional high-resolution NMR in a weakly ordered solvent (bicelles), and (ii) by solid-state NMR in multilamellar vesicles (MLV) formed by DMPC. Analysis of the experimental and MD-derived couplings in DMPC indicated that the force field used in the simulations reasonably well describes the experimental results with the exception for the glycerol fragment that exhibits significant deviations. The signs of dipolar couplings, not available from the experiments on highly ordered systems, were determined from the trajectory analysis. The crucial step in the analysis of residual dipolar couplings (RDCs) in TRH determined in a bicelle-environment was access to the conformational distributions derived from the MD trajectory. Furthermore, the conformational behavior of TRH, investigated by J-couplings, in the ordered and isotropic phases is essentially identical, indicating that the general assumptions in the analyses of RDCs are well founded.

Evaluation of electroporation-induced adverse effects on adipose-derived stem cell exosomes

“…Several studies have shown that trehalose is able to form hydrogen bonds with the phosphate groups of membranes, hereby mediating the replacement of water molecules-a process that is distinct from monosaccharides in stressful conditions (Pereira et al 2004;Villarreal et al 2004;Pereira and Hünenberger 2006;Kapla et al 2015). Other studies support another hypothesis, where trehalose acts in a vitrification process resulting in mechanical protection of the membrane (Koster et al 1994;Kapla et al 2013Kapla et al , 2015. Either way, trehalose is able to stabilize lipid membranes under stress, e.g.…”

Computational NMR of Carbohydrates: Theoretical Background, Applications, and Perspectives

“…It should be noted that very promising in the structural studies of carbohydrates is the application of molecular dynamics in combination with computational NMR, as exemplified in the paper by Kapla et al [ 153 ] dealing with the molecular dynamics simulations and NMR spectroscopical studies of trehalose. The authors investigated interactions between lipid membranes and trehalose using NMR spectroscopy and molecular dynamics computer simulations.…”

“…Corresponding surfaces are marked accordingly as ( a – f ). Reproduced from Sergeyev and Moyna [ 153 ] with the permission of Elsevier.…”

“…13 C-NMR chemical shift surfaces for the pairs of transglycosidic carbons in α-(1→1 ), β-(1→4 ), and α-(1→4 )-linked D-Glcp disaccharides as a function of the glycosidic bond dihedrals.Corresponding surfaces are marked accordingly as (a-f). Reproduced from Sergeyev and Moyna[153] with the permission of Elsevier.…”

“…Calculated and experimental (in parenthesis)13 C-NMR chemical shifts of different oligosaccharides in solid state. Compiled from Sergeyev and Moyna[153].…”