In all areas related to protein adsorption, from medicine to biotechnology to heterogeneous nucleation, the question about its dominant forces and control arises. In this study, we used ellipsometry and quartz-crystal microbalance with dissipation (QCM-D), as well as density-functional theory (DFT) to obtain insight into the mechanism behind a wetting transition of a protein solution. We established that using multivalent ions in a net negatively charged globular protein solution (BSA) can either cause simple adsorption on a negatively charged interface, or a (diverging) wetting layer when approaching liquid-liquid phase separation (LLPS) by changing protein concentration (c p) or temperature (T). We observed that the water to protein ratio in the wetting layer is substantially larger compared to simple adsorption. In the corresponding theoretical model, we treated the proteins as limited-valence (patchy) particles and identified a wetting transition for this complex system. This wetting is driven by a bulk instability introduced by metastable LLPS exposed to an ion-activated attractive substrate. Controlling and understanding protein adsorption is key to a number of phenomena in biomaterial science and medical devices such as biocompatibility, osseointegration, inflammation and contamination 1-3. One way to systematically study the underlying interaction mechanisms between proteins and solid surfaces is to alter the surface chemistry and topography e.g. through the use of alloys of different composition, self-assembled monolayers (SAMs), membrane bilayers, polymer brushes, smart biomaterials or tissue engineering 1,4-7. An interesting, and in fact efficient, alternative to modifying the surface properties would be to tune protein adsorption by exploiting suitable thermodynamic conditions, i.e. conditions that favour a certain level of adsorption driven by the underlying bulk phase behaviour. Adsorption at solid-liquid interfaces is the result of sufficiently attractive substrate-fluid and intermolecular fluid interactions. Strongly enhanced or macroscopic adsorption may in particular result in the vicinity of bulk instability regions, a phenomenon called 'wetting' that is mostly explored in the statistical physics of 'simple liquids' 8-10. Although the bulk phase behaviour of protein solutions shares intriguing similarities with that of suspensions of spherical colloids 11-14 , it is not clear a priori to what extent surface phenomena such as wetting can be transferred to solutions of proteins, in view of their significant complexity and patchy nature 15-22. Furthermore, the tailoring of adsorption beyond the monolayer would be of significant importance for the understanding of e.g. heterogeneous nucleation of crystals or for improving the biocompatibility of implants by pre adsorption, which makes this study not only important fundamentally, but also for applications. Salts provide a versatile way to manipulate the interactions. Specifically, multivalent ions can induce novel effects at interfaces, going well b...

We study three-color Förster resonance energy transfer (triple FRET) between three spectrally distinct fluorescent dyes, a donor and two acceptors, which are embedded in a single polystyrene nanosphere. The presence of triple FRET energy transfer is confirmed by selective acceptor photobleaching. We show that the fluorescence lifetimes of the three dyes are selectively controlled using the Purcell effect by modulating the radiative rates and relative fluorescence intensities when the nanospheres are embedded in an optical Fabry–Pérot microcavity. The strongest fluorescence intensity enhancement for the second acceptor can be observed as a signature of the FRET process by tuning the microcavity mode to suppress the intermediate dye emission and transfer more energy from donor to the second acceptor. Additionally, we show that the triple FRET process can be modeled by coupled rate equations, which allow to estimate the energy transfer rates between donor and acceptors. This fundamental study has the potential to extend the classical FRET approach for investigating complex systems, e.g., optical energy switching, photovoltaic devices, light-harvesting systems, or in general interactions between more than two constituents.