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

Abstract

We summarize and compare recent Molecular Dynamics simulations on the interactions of dipalmitoylphosphatidylcholine (DPPC) bilayers in the liquid crystalline phase with a number of small molecules including trehalose, a disaccharide of glucose, alcohols, and dimethylsulfoxide (DMSO). The sugar molecules tend to stabilize the structure of the bilayer as they bridge adjacent lipid headgroups. They do not strongly change the structure of the bilayer. Alcohols and DMSO destabilize the bilayer as they increase its area per molecule in the bilayer plane and decrease the order parameter. Alcohols have a stronger detrimental effect than DMSO. The observables which we compare are the area per molecule in the plane of the bilayer, the membrane thickness, and the NMR order parameter of DPPC hydrocarbon tails. The area per molecule and the order parameter are very well correlated whereas the bilayer thickness is not necessarily correlated with them.

Molecular dynamics simulations of microstructure and mixing dynamics of cryoprotective solvents in water and in the presence of a lipid membrane

“…The results shown that ethanol interacts with a POPC membrane primarily via hydrophilic interactions, in particular due to the formation of hydrogen-bonds to the lipid phosphate group. A recent MD investigation has also supported these results and shows that shortchain alcohols exhibit some preference to occupy regions near the upper part of the lipid acyl chains and the phosphatidylcholine headgroups [33,34,61,62]. Additionally, it has been shown that, in a homologous series of aliphatic n-alcohols with an intermediate chain length, an increase in the number of carbon atoms of an alkyl chain (butanol, pentanol and hexanol) results in a gradual decrease in hydrophilic solute-membrane interactions, so that a partitioning process and packing of solute molecules in alcohol/membrane/water systems are driven mainly by hydrophobic forces [63,64].…”

Morphological investigations of disaccharide molecules for growth inhibition of ice crystals

“…Some previous simulation studies (e.g., [2,17]) have suggested that disaccharide molecules tend to stabilize the structure of the phospholipids bilayer since they bridge adjacent lipid head groups and preserve the membrane under cooling conditions without affecting its structure. The precipitation phenomenon renders this process effective due to the enhancement of the contact between the cell membrane and a large concentration of disaccharide molecules.…”

The Effect of Methanol on Lipid Bilayers: An Atomistic Investigation

“…37,43 It has been long known that the molecular dynamic (MD) simulations are well suited for detailed analysis of the interaction between lipid bilayers and various chemicals and there are some recent studies reporting on the interaction between lipid bilayers and small nonwater polar molecules. [1][2][3][4][5][6][7]10,12,[17][18][19]21,22,[27][28][29][30][31][32]36,[39][40][41][42][43][44]46 Clearly, a detailed description of these studies is beyond the scope of this communication. Of direct relevance to the current study, Patra et al 30 reported the structural changes of dipalmitoylphosphatidylcholine (DPPC) lipid membranes in the presence of relatively small molar fractions (below 1.0 mol%) of ethanol and methanol in water.…”