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Molecular dynamics simulations and NMR spectroscopy studies of trehalose-lipid bilayer systems
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
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2015 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 17, no 34, 22438-22447 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 17, no 34, 22438-22447 p.
National Category
Physical Chemistry
Research subject
Physical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-120651DOI: 10.1039/c5cp02472bISI: 000359971300074OAI: oai:DiVA.org:su-120651DiVA: diva2:853957
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationCarl Tryggers foundation Swedish National Infrastructure for Computing (SNIC)
Available from: 2015-09-15 Created: 2015-09-15 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Computer Simulations of Membrane–Sugar Interactions
Open this publication in new window or tab >>Computer Simulations of Membrane–Sugar Interactions
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Carbohydrate molecules are essential parts of living cells. They are used as energy storage and signal substances, and they can be found incorporated in the cell membranes as attachments to glycoproteins and glycolipids, but also as free molecules. In this thesis the effect of carbohydrate molecules on phospholipid model membranes have been investigated by the means of Molecular Dynamics (MD) computer simulations.

The most abundant glycolipid in nature is the non-bilayer forming monogalactosyldiacylglycerol (MGDG). It is known to be important for the membrane stacking typical for the thylakoid membranes in plants, and has also been found essential for processes related to photosynthesis. In Paper I, MD simulations were used to characterize structural and dynamical changes in a lipid bilayer when MGDG is present. The simulations were validated by direct comparisons between dipolar couplings calculated from the MD trajectories, and those determined from NMR experiments on similar systems. We could show that most structural changes of the bilayer were a consequence of lipid packing and the molecular shape of MGDG.

In certain plants and organisms, the enrichment of small sugars such as sucrose and trehalose close to the membrane interfaces, are known to be one of the strategies to survive freezing and dehydration. The cryoprotecting abilities of these sugar molecules are long known, but the mechanisms at the molecular level are still debated. In Papers II–IV, the interactions of trehalose with a lipid bilayer were investigated. Calculations of structural and dynamical properties, together with free energy calculations, were used to characterize the effect of trehalose on bilayer properties. We could show that the binding of trehalose to the lipid bilayer follows a simple two state binding model, in agreement with recent experimental investigations, and confirm some of the proposed hypotheses for membrane–sugar interactions. The simulations were validated by dipolar couplings from our NMR investigations of TRH in a dilute liquid crystal (bicelles). Furthermore, the assumption about molecular structure being equal in the ordered and isotropic phases was tested and verified. This assumption is central for the interpretation of experimentally determined dipolar couplings in weakly ordered systems.

In addition, a coarse grain model was used to tackle some of the problems with slow dynamics that were encountered for trehalose in interaction with the bilayer. It was found that further developments of the interaction models are needed to properly describe the membrane–sugar interactions. Lastly, from investigations of trehalose curvature sensing, we concluded that it preferably interacts in bilayer regions with high negative curvature.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University, 2016. 78 p.
Keyword
Molecular simulations, Molecular dynamics, Lipid bilayers, Carbohydrates, Biological membranes, Trehalose, Glycolipids, Membrane—sugar interactions
National Category
Physical Chemistry
Research subject
Physical Chemistry
Identifiers
urn:nbn:se:su:diva-127402 (URN)978-91-7649-363-2 (ISBN)
Public defence
2016-04-29, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Available from: 2016-04-06 Created: 2016-03-03 Last updated: 2017-02-20Bibliographically approved

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