Molecular Dynamics Simulation Study of the Interaction of Trehalose with Lipid Membranes

Abstract

The interactions of the cryoprotective agent trehalose with a lipid membrane made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine at 323 K were studied by means of molecular dynamics simulations. It was observed that trehalose binds to the phospholipid headgroups with its main axis parallel to the membrane normal. Trehalose establishes hydrogen bonds with the carbonyl and phosphate groups and replaces water molecules from the lipid headgroup. Notably, the number of hydrogen bonds (HBs) that the membrane made with its environment was conserved after trehalose binding. The HBs between lipid and trehalose have a longer lifetime than those established between lipid and water. The binding of the sugar does not produce changes either in the lipid area or in the lipid order parameter. The effect of trehalose on the dipole potential is in agreement with experimental results. The contribution of the different components to the membrane dipole potential was analyzed. It was observed that the binding of trehalose produces changes in the different components and the sugar itself contributes to the surface potential due to the polarization of its hydroxyl in the interface.

Reconciliation of opposing views on membrane–sugar interactions

“…The positive values of Γ 3 at low sugar show that the binding mode dominates under these conditions, and this is likely to reflect sugar-head group hydrogen bonding, as identified in several computational studies (see, e.g., refs. [21][22][23]. Recently, computational analysis of systems at low water contents (48) has suggested that this binding couples to an enlarged lateral area as also seen in this work.…”

“…Investigations of fully hydrated membranes show an interesting tendency to fall into two groups with mutually conflicting conclusions. Thus, many investigations have suggested direct (favorable) interaction of sugars and the phospholipid interface (16)(17)(18)(19)(20)(21)(22)(23), and it is obvious that such interactions could be the origin of sugar effects, for example, through interlocking of several lipids molecules that simultaneously hydrogen bond to the same disaccharide molecule (24). Other stabilizing consequences of sugar binding have been put forward, and in this paper, we collectively refer to this interpretation as the "interaction hypothesis."…”

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

“…This is proposed to keep the spacing between the individual lipids during dehydration, possibly explaining the favourable effects of trehalose in lyophilisation. 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.…”

Enhacement of the Viability of <i>Lactobacillus</i> <i>plantarum</i> during the Preservation and Storage Process Based on the Response Surface Methodology

“…Some sugars are recognized as protectors and used for the preparation of freeze-dried cultures. These sugars stabilize the cell membrane by a mechanism of replacement of water and a series of interactions between membrane phospholipids and sugars [21].…”