ZnO biointerfaces with serum albumin have attracted noticeable attention due to the increasing interest in developing ZnO‐based materials for biomedical applications. ZnO surface morphology and chemistry are expected to play a critical role on the structural, optical, and electronic properties of albumin‐ZnO complexes. Yet there are still large gaps in the understanding of these biological interfaces. Herein we comprehensively elucidate the interactions at such interfaces by using atomic force microscopy and nanoshaving experiments to determine roughness, thickness, and adhesion properties of BSA layers adsorbed on the most typical polar and non‐polar ZnO single‐crystal facets. These experiments are corroborated by force field (FF) and density‐functional tight‐binding (DFTB) calculations on ZnO‐BSA interfaces. We show that BSA adsorbs on all the studied ZnO surfaces while interactions of BSA with ZnO are found to be considerably affected by the atomic surface structure of ZnO. BSA layers on the (0001‾) surface have the highest roughness and thickness, hinting at a specific upright BSA arrangement. BSA layers on (101‾0) surface have the strongest binding, which is well correlated with DFTB simulations showing atomic rearrangement and bonding between specific amino acids (AAs) and ZnO. Besides the structural properties, the ZnO interaction with these AAs also controls the charge transfer and HOMO‐LUMO energy positions in the BSA‐ZnO complexes. This ZnO facet‐specific protein binding and related structural and electronic effects can be useful for improving the design and functionality of ZnO‐based materials and devices.

Properties and functions of various ZnO materials are intensively investigated in biological systems for diagnostics, therapy, health risks assessment as well as bactericidal and decontamination purposes. Herein, the interface between ZnO and biological environment is studied by characterizing adsorption of bovine serum albumin (BSA) and fetal bovine serum (FBS) using atomic force microscopy with CF4‐treated tips. Similar molecular morphologies (thickness around 2 nm) yet different binding forces to ZnO (10–25 nN) are observed. These observations are corroborated by atomic scale simulations of BSA on (0001) ZnO surface using force‐field method and showing rearrangements of Zn surface atoms. Such binding may have an impact also on other properties of ZnO–BSA complex.

Despite the importance of thiorphan as a small molecule with vital biological roles, its interactions with zinc oxide (ZnO) nanomaterials that are prospective in drug delivery and theranostic applications have not yet been sufficiently explored.Here the impact of surface polarity of different ZnO facets on thiorphan adsorption is studied both experimentally by atomic force microscopy (AFM) and angle resolved X-ray photoelectron spectroscopy (XPS) and theoretically by force field molecular dynamics (FFMD) and density functional tight binding simulations (DFTB). Polar ZnO surfaces cause the formation of thiorphan nanodots, where the size of the nanodots depends on the direction of dipoles: small (4 nm) nanodots are formed on Znface ZnO, while large (25 nm) nanodots are formed on O-face ZnO. Nonpolar ZnO surfaces cause self-assembly into layered nanoislands with characteristic 4 nm layer thickness, which subsequently merge into rigid nanolayers. The self-assembly is shown to be controlled solely by the effect of surface dipole electric field orientation and magnitude, whereas effects of surface chemistry or solution are negligible. The results thus also show a way for controlling the assembly of thiorphan and other molecular nanomaterials for diverse applications.

We studied the interactions of bovine serum albumin (BSA) molecule with ZnO surfaces by force field simulations. The different orientations of BSA over the two main nonpolar wurtzite ZnO surfaces (10 1 ¯ 0) and (11 1 ¯ 0) have been investigated. These surfaces contain both Zn and O atoms. We compare the results also with polar Zn-face (0001) surface. The results demonstrate tendency of BSA molecule for being adsorbed on the ZnO surface in specific orientations. This happens either by bonding between a hydrogen atom of BSA molecule to an oxygen atom of the ZnO surface or by physical attraction inducing ZnO atoms displacement in some cases.

The Cover Feature illustrates how bovine serum albumin binds to polar and non‐polar ZnO single‐crystal facets via its specific amino acids. Atomic scale calculations using density‐functional tight‐binding models are shown in the circles for specific binding cases, depending also on ZnO facet orientations. More information can be found in the Article by Hadi Hematian and co‐workers.