Nanoparticle-mediated interactions governing thermal gelation of protein dispersions with tunable properties

Nanoparticle-protein dispersions constitute complex soft materials in which competing attractive and repulsive interactions can strongly influence their phase behavior, including gelation. In this work, we demonstrate a strategy to utilize interaction between anionic silica nanoparticles and anionic protein bovine serum albumin to achieve heat-induced gels with tunable physical properties. Upon heating, the protein molecules in solution undergo unfolding followed by hydrophobic aggregation, leading to the formation of a three-dimensional gel network. The introduction of negatively charged nanoparticles generates additional electrostatic repulsion that competes with the attractive hydrophobic interactions between partially unfolded proteins. This competition modifies both the structure and mechanical properties of the resulting gels. In particular, nanoparticle-protein gels exhibit markedly enhanced optical transparency (∼90%) compared with gels formed from pure protein solutions (<1%). Rheological measurements further show shear-thinning behavior, with the gel strength decreasing systematically with increasing nanoparticle concentration, leading to progressively softer gels. At sufficiently high nanoparticle content, gelation is completely suppressed, thereby stabilizing the protein dispersion against thermal aggregation. The underlying mechanism is elucidated in terms of interaction potentials obtained by modeling small-angle neutron scattering data measured in situ during gel formation. Finally, we demonstrate that nanoparticle concentration and ionic strength serve as effective parameters to control gel opacity and mechanical rigidity, enabling the formation of both soft and rigid gels. These results demonstrate how nanoparticle-mediated interactions can regulate aggregation and gelation in protein-based soft matter systems.