Different mechanisms on the stabilization of POPC membrane by trehalose upon varied mechanical stress

Abstract

Trehalose has been proven to be able to protect the membrane from being damaged by dehydration. Since dehydration is accompanied by large mechanical stress, it is meaningful to study the effect of trehalose on the membrane subject to lateral stress for understanding its protective mechanism. In present work, molecular simulations were performed on the POPC bilayers with different amount of trehalose under lateral pressure and tension. The results indicate that trehalose invariably induces increase in the area per lipid Axy and decrease in bilayer thickness hz and ordering degree |SCD|, which mean improved structure of membrane. However, the main roles trehalose plays are slightly different in stabilizing compressed and expanded membrane. Under tensile stress, the water replacement effect plays a leading role. Trehalose reaches as deep as water into the bilayer. Hydrogen bonds (H-bonds) forming between trehalose and lipid compensate the reduction of water-lipid H-bonds. More trehalose will replace more water to form H-bonds with lipid and help to hold the structure together through abundant H-bond bridges of various patterns. Under lateral pressure, the replacement of water is limited since trehalose only interacts with the bilayer surface zone. The sum of water-lipid (W-L) and trehalose-lipid (T-L) H-bond reduces upon addition of trehalose. Nevertheless, the penetration depth of water increases in the presence of trehalose while WL H-bonds become less. At the same time, WL H-bonds lifetime is significantly extended. These facts suggest that water forming H-bonds with phosphate and carbonyl oxygen and locating in bilayer interior is trapped by trehalose which is closer to surface and has longer H-bonds lifetime. It can be speculated that the residual water maintains the effective hydration level and the low ordering degree of membrane. This effect is similar to Water entrapment which takes place in the stabilization of protein by trehalose. Moreover, the presence of trehalose increases the viscidity of the system and makes it easy to vitrify. The membrane becomes stiffer and has more resistance to deformation from the perspective of Ka. The vitrification mechanism is not excluded whether the membrane is compressed or stretched. Our findings could provide some insights in the design of protecting agents and processes.