Direct Visualization of Contrasting Hydration Structures on Poly(2-methoxyethyl acrylate) and Poly(n-butyl methacrylate) by Frequency Modulation Atomic Force Microscopy.

Interfacial hydration governs the biological response of polymeric biomaterials, yet directly visualizing solvation structures on soft, fluctuating polymer surfaces has remained experimentally challenging. Here we employ ultralow-noise frequency modulation atomic force microscopy (FM-AFM) to resolve the nanoscale hydration structures of blood-compatible poly(2-methoxyethyl acrylate) (PMEA) and protein-adsorbing poly(n-butyl methacrylate) (PBMA) in phosphate-buffered saline. Subnanometer frequency shift mapping combined with nanomechanical analysis reveals two distinct water architectures. PBMA shows a static multilayered structure with 0.30 nm periodicity, typical of hydrophobic surfaces such as graphite. In contrast, PMEA is exceptionally soft (apparent modulus E* ≈ 100 MPa) and, despite being fully hydrated, shows no detectable layering. We assign this absence of layering to a dynamically fluctuating, water-penetrated side-chain ("intermediate water") region, which has been proposed to act as a physical barrier against irreversible protein adsorption. Direct FM-AFM access to hydration structures at polymer-water interfaces should guide the design of blood-compatible biomaterials.