Small Angle Neutron Scattering Studies of Protein Aggregation

Understanding protein aggregation is important for many areas, including the improvement of processing and formulation of biopharmaceuticals, elucidating the mechanism of neurodegenerative diseases and manufacturing novel biomaterials. Of particular interest is the nucleation stage of aggregation, which is not well understood.
The initial nucleation of protein aggregates has proved elusive due to the small size scales at which they form, and the rapid time period that this occurs in. Here we present the small angle neutron scattering data collected at D22 beamline at Institut Laue-Langevin, Grenoble. This provided time resolved information on the nanoscale on bovine serum albumin (BSA) which was used as a model system for studying aggregation processes. Using a dual population scattering model to characterise the presence of both monomer and aggregate populations, we observed two distinct aggregation stages; a nucleation phase followed by growth phase. During the nucleation phase, a stable population of aggregates was established. This was followed by a growth phase, characterised by aggregates increasing in size. This behaviour is examined across a temperature range, where an increase in temperature increases both the rate and the size of the aggregate nuclei. Work contained here presents a novel approach to examining the process of protein aggregation on the nanoscale.