Molecular-scale structures of the surface and hydration shell of bioinert mixed-charged self-assembled monolayers investigated by frequency modulation atomic force microscopy.

We studied the surface structure and hydration structure of a bioinert mix-charged self-assembled monolayer (MC-SAM) comprised of sulfonic acid (SA)- and trimethylamine (TMA)-terminated thiols in liquid by frequency modulation atomic force microscopy (FM-AFM) at a molecular-scale. The TMA end groups showed a highly-ordered rectangular arrangement on a gold substrate in phosphate buffer saline (PBS). Highly structured water was observed at the interface of the MC-SAM and PBS, whereas a less structured hydration structure was observed on bioactive SAMs such as those with OH- and COO- terminal groups. Differences in surface and interface structures between the bioactive and bioinert SAMs suggest that the highly structured water at the bipolar MC-SAM surface works as a physical barrier to prevent adsorption or adhesion of protein and cells. Our results led to the idea that the hydration structure is an important factor in the determination of interactions between SAMs and biomolecules.