Structural characterization of protein-polymer conjugates for biomedical applications with small-angle scattering

Protein-polymer conjugates, typically consisting of one or more polymers covalently attached to a protein, are an increasingly common component in biotechnology. Polymers can increase circulation time, alter immune responses, and influence the self-assembly of proteins to which they are attached. To understand and take full advantage of the benefits that protein-polymer conjugates provide, there is a strong need for structural characterization of both the conjugates and their self-assembled structures. Although X-ray crystallography is suitable for determining protein structure, protein-polymer conjugates do not generally crystallize, requiring the use of alternative techniques. Small-angle scattering, with neutrons in particular, is one such technique. In this article, we review recent work in the area of protein-polymer conjugates and highlight the important role that structure plays. We then highlight shape-dependent and shape-independent approaches for structural characterization of protein-polymer conjugates and future directions in small-angle scattering interpretation. We conclude by introducing a new model that we suggest may be useful in the future to acquire more detailed structural properties.