Molecular dynamics simulations for microscopic behavior of water molecules in the vicinity of zwitterionic self-assembled monolayers

Zwitterionic biomaterials, such as phosphobetaine polymers,¹ have been widely used because of their excellent biocompatibility, which results from suppression of nonspecific protein adsorption and cell adhesion.^{2, 3, 4, 5} To understand fundamentally how the biocompatible materials can prevent protein adsorption at the molecular level, significant efforts have been made by experimental approaches. Ishihara et al.¹ investigated the hydration of zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers, indicating that MPC can hold water molecules strongly. Feng et al.² suggested that the water layer above the MPC surface does not change the native conformation of adsorbed proteins. Kitano et al.³ concluded that a 1-carboxy-N,N-dimethyl-N-(2′-methacryloyloxyethyl)methanaminium inner salt (CMB) monomer does not change the hydrated structure of water molecules. These experimental reports have suggested that the structure of water in the vicinity of zwitterionic biomaterials definitely influences suppression of protein adsorption.

Molecular dynamics (MD) simulations have also been a powerful approach for evaluating the molecular behaviors in various fields,^{6, 7} including protein adsorption phenomena on various material surfaces.^{8, 9, 10, 11} Chen et al.⁸ reported the strong resistance of zwitterionic phosphorylcholine (PC) self-assembled monolayers (SAMs) to protein adsorption. He et al.⁹ also investigated the antifouling properties of PC SAMs by MD simulations. They suggested that their strong resistance to biofouling results from their capacity for hydration via electrostatic interactions. Water molecules in the vicinity of the SAM surface probably act to produce a strong repulsive force on the approaching protein, because of a tightly bound water layer. They also suggested that these tightly bound layers are due to the ionic solvation nature of zwitterionic head groups, by comparing with the data obtained for a nonionic oligo(ethylene glycol) (OEG) SAM surface. The PC and OEG SAMs are found to be quite different in the antifouling mechanisms. Water molecules in the hydration layer near the PC SAM surface stay longer than those on the OEG SAM surface. This means that water molecules are more tightly bound on the PC SAM surface. Furthermore, the water molecules near the PC SAM surface is much more randomly oriented, which is close to bulk water. They conclude that the PC SAM surface binds water by ionic electrostatic interactions more strongly than the hydrophilic and neutral OEG SAM surface, where water molecules are more loosely bound via hydrogen bonding.

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