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

TL;DR

This study uses extensive molecular dynamics simulations to reveal that carbohydrate-carbohydrate interactions, such as LeX and Lac 2, are weak, fuzzy, and generic, providing detailed insights into membrane adhesion processes.

Contribution

It demonstrates that carbohydrate interactions are weak and fuzzy, offering a detailed atomistic understanding validated against experimental data.

Findings

LeX-LeX interactions are fuzzy and involve multiple short-lived conformations.

Association constants for LeX and Lac 2 match experimental results.

Carbohydrate interactions are weak and generic across different small neutral carbohydrates.

Abstract

Carbohydrates such as the trisaccharide motif LeX 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 LeX, 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 LeX-LeX interactions in solution and during membrane adhesion. In this picture, the LeX-LeX interactions are fuzzy, i.e. LeX 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 LeX. The fuzzy, weak carbohydrate-carbohydrate interactions quantified in our simulations thus appear to be a generic feature of small, neutral carbohydrates such as LeX and Lac 2.