Written in Water: Hydration Repulsion Governs Selective Protein Adsorption on Saccharide Self-Assembled Monolayers.

Saccharide-based materials are essential in bioinspired design, yet their mechanisms for resisting nonspecific protein adsorption while permitting specific binding remain unclear. This study systematically explores the relationship between surface forces and protein adsorption on glucose (Glc), lactose (Lac), and maltose (Mal) self-assembled monolayers (SAMs). Surface-sensitive techniques revealed protein resistance in the order: Mal > Lac > Glc. Among the tested proteins, bovine serum albumin (BSA) showed the lowest adsorption, immunoglobulin G (IgG) was intermediate, and fibrinogen adsorbed the most, demonstrating saccharide-dependent selectivity. Measurements revealed these surfaces generate short-range repulsive forces in physiological buffer, caused by structured interfacial water layers. The key finding is a strong link between hydration repulsion and protein adsorption behavior. The structural features of saccharides influence their interfacial water organization through hydrogen bonding, which controls resistance to nonspecific adsorption. Overall, the interfacial water acts as a dynamic barrier against protein binding. Analysis of mixed-charge residue pairs (glutamic acid-lysine and aspartic acid-lysine) on proteins, combined with potential saccharide recognition sites, suggests selective adsorption results from interplay between protein surface chemistry and interfacial hydration. This work clarifies hydration repulsion mechanisms on saccharide surfaces, establishes quantitative relationships between structure, hydration, and performance, and provides design principles for advanced biomaterials.