The understanding of protein behaviour at the nanoscale is critical for the development of new therapies and biosensing. The assembly of peptides for new therapies are performed on the surface of a biosensor and because of the rough nature of this sample, the characterisation is usually performed on a separate substrate that will provide a higher contrast with a different technique. The ideal scenario is for the same surface to be used in both sensing and characterisation stages. For biosensing, the rough nature of the surface could increase the range of mass measurement for biosensors with micro and nanoscale surfaces. Additionally, the interaction of proteins with nanostructures open the possibility of altering the dynamics of protein adsorption. These changes could be translated to different mechanical properties of the sensed protein. Furthermore, the induced conformational change might allow for a permanent attachment of the protein, increasing the limit of detection of a biosensor. However, the behaviour of proteins with nanoscale features is not well understood. Therefore, the fabrication of nanostructured surfaces along with eliminating such features on QCM biosensors for sensing and characterisation of proteins is pursued in this dissertation. Multiple novel methods of nanofabrication on top of QCM gold electrodes were created using ZnO nanowires (Chapter 1), gold nanoparticles (Chapter 2), and e-beam lithography (Chapter 5). These techniques were further optimised to obtain simple protocols to be followed by any user. Subsequently, optimal surfaces were used for protein adsorption and their results show less protein adsorption than the expected by the area increase of the features (50-70%), suggesting protein conformational changes (spreading) upon binding. The observation of protein conformational changes on nanostructures suggested that the roughness of standard gold QCM electrodes might also play a role in protein adsorption. A novel fabrication process is developed for the transfer of an atomically flat surface of gold onto a QCM Au electrode, the pressure-forming template stripped (PTS) technique. In Chapter 3, the PTS method is presented with the crucial parameters for obtaining an atomically flat gold surface on QCM resonators and their optimisation to obtain a roughness of 0.35 nm ± 0.05 root mean square and a required thickness of 100 nm of Au QCM electrodes. Furthermore, the QCM with PTS electrodes (PTS QCM) is used to adsorb model protein bovine serum albumin (BSA). This is compared against resonators with a standard electrode roughness from different companies, and against resonators build in-house with higher roughness than commercial samples. It is showed by both QCM mass monitoring and AFM of the same PTS QCM sample that BSA adsorption of BSA occurs in a self-assemble like manner, a tightly packed monolayer. More BSA areal mass is adsorbed on PTS QCM (15%) and high roughness QCM (17%) resonators than QCM samples with standard roughness. In contrast with standard QCM, high roughness QCM resonators induce aggregates on the surface increasing the mass adsorbed and obtaining similar areal mass to the tightly packed adsorption on PTS QCM devices.