Interaction of the Disaccharide Trehalose with a Phospholipid Bilayer: A Molecular Dynamics Study

Abstract

The disaccharide trehalose is well known for its bioprotective properties. Produced in large amounts during stress periods in the life of organisms able to survive potentially damaging conditions, trehalose plays its protective role by stabilizing biostructures such as proteins and lipid membranes. In this study, molecular dynamics simulations are used to investigate the interaction of trehalose with a phospholipid bilayer at atomistic resolution. Simulations of the bilayer in the absence and in the presence of trehalose at two different concentrations (1 or 2 molal) are carried out at 325 K and 475 K. The results show that trehalose is able to minimize the disruptive effect of the elevated temperature and stabilize the bilayer structure. At both temperature, trehalose is found to interact directly with the bilayer through hydrogen bonds. However, the water molecules at the bilayer surface are not completely replaced. At high temperature, the protective effect of trehalose is correlated with a significant increase in the number of trehalose-bilayer hydrogen bonds, predominantly through an increase in the number of trehalose molecules bridging three or more lipid molecules.

Structural effects of small molecules on phospholipid bilayers investigated by molecular simulations

“…found very similar effects [24]. The area per molecule is almost unaffected even with 128 molecules of trehalose for 128 molecules of DPPC.…”

“…More recently computational studies of mixtures of various phospholipids [12,13,14,15] and of phospholipids with cholesterol [16,17,18,19] have also been reported. However, the question how such lipid bilayer membranes interact with small molecules has to date not gained very much attention except for a few initial studies on alcohols [20,21,22], sugars [23,24], and dimethylsulfoxide (DMSO) [25,26]. The influence of lipophilic polymers on lipid bilayers has also been studied [27].…”

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

“…It is found in organisms like insects, yeast and fungi; organisms that tend to accumulate trehalose under stressful conditions like anhydrobiosis, heat shock or osmotic stress to a greater degree than any other known sugars. Several studies have shown that trehalose could stabilize membranes and proteins under unfavourable conditions (Pereira et al 2004). Based on these characteristics, trehalose has been examined for its favourable effects on human cells and biostructures undergoing stress, e.g.…”

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

“…There are several molecular features that govern the behavior of a drug in cell membranes such as size, shape, solubility, hydrophilicity, lipophilicity, and pK a , among others. Previously, many authors have reported studies of the interaction of drugs and membrane models with experimental technics (Nunes et al 2011;Lucio et al 2009;Fuchs et al 1990) and molecular dynamic (MD) simulations (Robinson et al 1995;Gabdouline et al 1996;Smondyrev andBerkowitz 1999, 2001;Hofsäß et al 2003;Pereira et al 2004;Falck et al 2006;Högberg et al 2007;Seddon et al 2009;Sirk et al 2009;Boggara and Krishnamoorti 2010;Witzke et al 2010;Orsi andEssex 2010, Koukoulitsa et al 2011;Nitschke et al 2012;Poger and Mark 2013;Loverde 2014;Jalili and Saeedi 2016). In particular, studies based on drug partitioning in lipid bilayers and the thermodynamics of drug/lipid interaction have great importance in understanding the reaction mechanisms of antitumor drugs and to design new cell membrane-targeted drugs (Boggara and Krishnamoorti 2010;Jendrossek and Handrick 2003;Goldstein et al 2011;Choi et al 2013).…”