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Nanoparticles are promising platforms for biomedical applications ranging from diagnostic tools to therapeutic delivery agents. During the course of these applications, nanoparticles are exposed to a complex mixture of extracellular serum proteins that nonspecifically adsorb onto the surface. The resulting protein layer, or protein "corona," creates an interface between nanoparticles and the biological environment. Protecting the nanoparticle surface can reduce protein adsorption, but complete inhibition remains a challenge. As a result, the corona, rather than the nanoparticle itself, mediates the cellular response to the nanoparticle. The following dissertation describes the fundamental characterization of the cellular binding of charged nanoparticles, interactions of protein-nanoparticle complexes with cellular receptors, and the structural and thermodynamic properties of adsorbed corona proteins.

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Ge₂Sb₂Te₅ (GST) is an established phase-change material that undergoes fast reversible transitions between amorphous and crystalline states with a high electro-optical contrast, enabling applications in non-volatile optical and electronic memories and optically-switchable structured metamaterials. This work demonstrates that optical anisotropy can be induced and recorded in pure and doped GST thin films using circularly polarised light (CPL), opening up the possibility of controlled induction of anisotropic phase transition in these and related materials for optoelectronic and photonic applications. While the amorphous-to-crystalline phase transition in GST has generally been understood to proceed via a thermal mechanism, significant optical anisotropy (measured by circular dichroism (CD) spectroscopy in this work) strongly suggests that there is an electronic athermal component of the phase change induced by the handedness of circularly polarised nanosecond laser pulses and implies the existence of chiral structures or motifs. Optically active and inactive regions in the films have also been studied using X-ray and electron diffraction and spectroscopic techniques in order to obtain a structural picture that can be correlated to the optical changes observed and the findings offer surprising evidence of the nature of the phase transition. Regions exhibiting higher CD signal intensities were found to be mostly amorphous with elemental phase separation observed within modified surface features. Several mechanisms are proposed for the observed phenomena, including the retention of chiral crystalline fragments in laser- irradiated and melt-quenched amorphous regions, which could explain the results of CD spectroscopy. This may be extended to other material systems and harnessed in potential metamaterials, plasmonics, photonics or chiroptical applications.

Thermal stability is an important and interesting physical property of proteins. A common method to study it by is circular dichroism (CD) spectroscopy. The aim of this study was to test methods to improve thermal stability analysis by CD spectroscopy. Experiments were performed using the Abp1p SH3 domain from yeast as a model protein. Thermal denaturation was monitored at multiple wavelengths. It was concluded that for data sets of reasonable quality the choice of wavelength does not affect the results. An approach to estimate stability of thermophilic proteins was tested where thermal stability was measured at different concentrations of the denaturant GuHCl. The thermochemical data was used to estimate the stability in absence of GuHCl by extrapolation. The results were compared to those obtained from CD spectroscopy and differential scanning calorimetry. It was found that a stabilizing effect from low concentrations of GuHCl complicated the extrapolation. It is likely that this method is more successful if there is no stabilizing effect. The effect of ΔCp in stability parameter calculations was investigated with an experimentally and theoretically determined ΔCp. This was further investigated with synthetic data sets. The ΔCp used in calculations had no notable effect, as long as there was no cold denaturation. Although ΔCp is not necessary in calculations, it is an interesting parameter itself. ΔCp can be calculated from the thermochemical data used for extrapolation. The results in this study demonstrate robustness in thermal stability analysis by CD spectroscopy and a potential for development.

Alzheimer’s disease is an incurable neurodegenerative disorder linked to the amyloid β (Aβ) peptide, a 38-43 residue peptide. The detailed molecular disease mechanism(s) is (are) unknown, but oligomeric Aβ structures are proposed to be involved. In common for the papers in this thesis is interactions; interactions between Aβ(1-40) and selected molecules and metal ions. The purpose has been to find out more about the structural states that Aβ can adopt, in particular the β-sheet state, which probably is linked to the oligomeric structures. The methods used have been nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence spectroscopy using Thioflavin T (ThT). Upon addition of SDS/LiDS detergent or Congo red (CR) to Aβ(1-40), the initial random coil/PII-helix state was transformed into β-sheet and, in the case of detergent, a final α-helical state. In contrast to SDS/LiDS and CR, the dimeric Affibody molecule locks monomeric Aβ(1-40) in a β-hairpin state. It was found that by truncating the flexible N-terminal end of the Affibody molecule its affinity to Aβ was improved. The aggregation of Aβ(1-40) was further studied in the presence of a β-cyclodextrin dimer by a kinetic assay using ThT. Although having a weak dissociation constant in the millimolar range, the β-cyclodextrin dimer modified the aggregation pathways of Aβ. Finally Aβ(1-40) was studied in presence of Cu2+ and Zn2+ at physiological and low pH. Cu2+ was observed to maintain its specific binding to Aβ when decreasing the pH to 5.5 while Zn2+ behaved differently. This could be of importance in the Alzheimer’s disease brain in which the environment can become acidic due to inflammation.        In conclusion the results show that Aβ(1-40) is very sensitive to its environment, responding by adopting different conformations and aggregating in aqueous solutions. The β-sheet state is induced by varying molecules with different properties, properties that govern the final Aβ state. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 5: Manuscript.