Weak carbohydrate–carbohydrate interactions in membrane adhesion are fuzzy and generic

Abstract

Carbohydrates such as the trisaccharide motif Le^X are key constituents of cell surfaces. Despite intense research, the interactions between carbohydrates of apposing cells or membranes are not well understood. In this article, we investigate carbohydrate–carbohydrate interactions in membrane adhesion as well as in solution with extensive atomistic molecular dynamics simulations that exceed the simulation times of previous studies by orders of magnitude. For Le^X, we obtain association constants of soluble carbohydrates, adhesion energies of lipid-anchored carbohydrates, and maximally sustained forces of carbohydrate complexes in membrane adhesion that are in good agreement with experimental results in the literature. Our simulations thus appear to provide a realistic, detailed picture of Le^X–Le^X interactions in solution and during membrane adhesion. In this picture, the Le^X–Le^X interactions are fuzzy, i.e. Le^X pairs interact in a large variety of short-lived, bound conformations. For the synthetic tetrasaccharide Lac 2, which is composed of two lactose units, we observe similarly fuzzy interactions and obtain association constants of both soluble and lipid-anchored variants that are comparable to the corresponding association constants of Le^X. The fuzzy, weak carbohydrate–carbohydrate interactions quantified in our simulations thus appear to be a generic feature of small, neutral carbohydrates such as Le^X and Lac 2.