Do α, α-(1-1)-Linked Disaccharides Enhance Stability of the Lipid Bilayer more than α, β-Linked Disaccharides under Desiccation?

Disaccharides play a crucial role in protecting biological membranes from desiccation. Previous studies suggest that disaccharides with α,α-(1-1) glycosidic linkages, which adopt a clamshell conformation in the crystalline phase, are more effective under dry conditions than those with α,β-glycosidic linkages, which have an open structure. However, their relative effectiveness under hydrated conditions remains unclear. To address this, we conducted molecular dynamics (MD) simulations of E. coli lipid membranes across hydration levels (h = 42 to 2) in the presence of α,α-galacto-trehalose and α,β-trehalose, comparing them with previously studied sucrose and α,α-trehalose. This selection allows us to evaluate the role of glycosidic linkages under varying hydration. Our results reveal that in the presence of even minimal water, all four disaccharides exhibit similar membrane-stabilizing effects, mitigating desiccation-induced stress by reducing lipid-lipid interactions and preventing excessive lipid packing. The structural advantage of α,α-(1-1)-linked sugars observed in the crystalline phase does not persist under hydrated conditions. These findings provide molecular-level insights into the protective mechanisms of disaccharides, suggesting that organisms may accumulate different sugars not necessarily for their intrinsic superiority but for availability and metabolic adaptability. This study refines our understanding of sugar-mediated membrane stabilization under desiccation stress, offering a broader perspective on the selection of protective solutes in biological systems.