SANS Partial Structure Factor Analysis for Determining Protein-Polymer Interactions in Semidilute Solution

Protein-polymer interactions play a crucial role in many processes, including protein crystallization, biofouling, and self-assembly of protein-polymer bioconjugates. However, it is often difficult to measure these interactions in multicomponent systems, especially in semidilute solutions. Here, contrast-variation small-angle neutron scattering (CV-SANS) was used to quantify the interactions between three water-soluble polymers (PNIPAM, POEGA, and PDMAPS) and a model protein mCherry. CV-SANS enables decomposition of SANS intensities into partial structure factors that describe polymer-polymer, protein-protein, and polymer-protein interactions. The three polymers span various chemistries and properties, with PNIPAM and POEGA being non-ionic polymers with different hydrogen-bonding capabilities and PDMAPS being a zwitterionic polymer. PNIPAM/mCherry interactions were repulsive and dominated by depletion forces. In contrast, POEGA/mCherry interactions are attractive, with polymer enrichment at the protein surface. PDMAPS/mCherry interactions are more complex, with both depletion and electrostatic contributions. CV-SANS thus represents a powerful method to separate, quantify, and reveal the nature of interactions in multicomponent systems.