The solvent accessible surface area of proteins is very complex, mainly because it is composed of domains with different degrees of affinity for water. The domains nature and arrangement determine both the interactions of the proteins with water (and therefore the water structure around the protein) as well as the interactions with other particles in suspension (other proteins or other macromolecules). Both these interactions are fundamental to determine the functionality of the proteins. To date, a theoretical model able to predict the wetting properties of proteins has yet to be developed. The goal of this thesis is to improve our understanding of the wetting properties of this kind of complex surfaces. In order to simplify the interpretation of the results a model system has been used: gold nanoparticles protected by a shell composed of a binary mixture of hydrophobic/hydrophilic ligands. These nanoparticles resemble proteins because of their overall size as well as the size of the hydrophilic and hydrophobic domains exposed on their surface. The advantages of working with nanoparticles include the fact that they are stable over a larger range of conditions and that the properties of the ligand shell can be designed and tuned depending on the research question. In this thesis we show that the arrangement of the hydrophobic and hydrophilic domains is responsible for the interaction between the particles and the surrounding solvent (especially water). Indeed, we show that both the water structure and interfacial energy vary significantly between identical particles that differ only in the domain arrangement. A new predictive model is proposed. This model considers, for every molecule in the ligand shell, the contributions of its first-nearest neighbors as a descriptor to determine the wetting properties of the surface. The experiments and theoretical model proposed here provide a starting point to develop a comprehensive understanding of complex interfaces as well as for the engineering of synthetic ones. The interparticle interactions in water are also been characterized. It is shown that there exists the possibility to screen hydrophobic attraction by adding small molecules to the suspension. This stabilization technique seems to be relevant to maintain the stability of biological fluids. An example of the application of this stabilization technique to food science is also presented here. In addition to these studies, an innovative technique to measure the surface energy at the nanoscale is presented here, based on the measurement of the adhesion force between an atomic force microscopy tip and a sample.