Water-mediated interactions between glycans are weakly repulsive and unexpectedly long-ranged

Abstract

Glycans on the cell surface play an essential role in mediating cell-cell interactions as well as immune response. Despite their importance, interactions between them have not been fully characterized. Here, we reveal, using all-atom molecular dynamics simulations and free energy calculations, that water-mediated interactions between a pair of N-glycans without net charge are weakly repulsive with a range that exceeds their sizes. Unexpectedly, the effective glycan-glycan interactions decay logarithmically as the separation between them increases. Strikingly, this finding coincides exactly with the predicted interaction, which is entropic in origin, between two star polymers, consisting of long flexible polymers grafted onto colloidal particles. The weak repulsive interaction, which extends beyond the size of a glycan, is sensitive to the relative orientation of the glycans. The effective long-range repulsive interaction vanishes if the charges on water are turned off, thus establishing that electrostatic interactions, arising in part due to the persistent hydrogen bonds between water and the glycans, are responsible for the inter-glycan repulsion.