Assessment of structure factors for analysis of small-angle scattering data from desired or undesired aggregates

Abstract

Aggregation processes are central features of many systems ranging from colloids and polymers to inorganic nanoparticles and biological systems. Some aggregated structures are controlled and desirable, e.g. in the design of size-controlled clustered nanoparticles or some protein-based drugs. In other cases, the aggregates are undesirable, e.g. protein aggregation involved in neurodegenerative diseases or in vitro studies of single protein structures. In either case, experimental and analytical tools are needed to cast light on the aggregation processes. Aggregation processes can be studied with small-angle scattering, but analytical descriptions of the aggregates are needed for detailed structural analysis. This paper presents a list of useful small-angle scattering structure factors, including a novel structure factor for a spherical cluster with local correlations between the constituent particles. Several of the structure factors were renormalized to get correct limit values in both the high-q and low-q limit, where q is the modulus of the scattering vector. The structure factors were critically evaluated against simulated data. Structure factors describing fractal aggregates provided approximate descriptions of the simulated data for all tested structures, from linear to globular aggregates. The addition of a correlation hole for the constituent particles in the fractal structure factors significantly improved the fits in all cases. Linear aggregates were best described by a linear structure factor and globular aggregates by the newly derived spherical cluster structure factor. As a central point, it is shown that the structure factors could be used to take aggregation contributions into account for samples of monomeric protein containing a minor fraction of aggregated protein. After applying structure factors in the analysis, the correct structure and oligomeric state of the protein were determined. Thus, by careful use of the presented structure factors, important structural information can be retrieved from small-angle scattering data, both when aggregates are desired and when they are undesired.