Molecular investigation of the interactions of trehalose with lipid bilayers of DPPC, DPPE and their mixture

Molecular dynamics simulations were performed to study structural and dynamic properties of fully hydrated pure and mixed bilayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) in the presence of trehalose (5 wt%). Simulations were performed for 50 ns at 350 K and 1 bar in the liquid-crystalline state of the lipid bilayers. At the concentration considered, the effect of trehalose on pure and mixed DPPC/DPPE structure are minimal, with the area per headgroup and lipid tail order parameter unchanged compared to systems without trehalose. Density profiles indicate a larger concentration of trehalose near the interface, suggesting preferential binding of trehalose with the bilayer. Hydrogen bond analysis between trehalose and the bilayers shows that the largest number of interactions occurs with DPPC lipids, whereas the fewest interactions occur in a mixed 1: 1 DPPC/DPPE bilayer. The latter is a result of the inter and intramolecular binding of the amine group in DPPE, thus preventing trehalose from hydrogen bonding to the bilayer. For the pure DPPE bilayer, an excess of hydrogen-donors (amine groups) create a competitive hydrogen bonding environment that weakens lipid-lipid interactions and favors hydration of the amine groups, which enhances the binding of trehalose with the bilayer.