We study the effect of limited heat-induced aggregation of BSA on structure development in the
water–gelatin-thermally aggregated BSA (BSA) system. The pH is set at 5.4 and the temperature is
higher than the conformation transition temperature of gelatin, but lower than the denaturation temperature of BSA. Dynamic light scattering, circular dichroism, and fluorescence measurements are used to
monitor structure changes. Interaction of gelatin with BSA leads to formation of large complex particles
with an average radius ∼1500 nm. BSA–gelatin complex formation accompanies partial destabilization
of the secondary and tertiary structures of BSA and an additional exposure of hydrophobic tryptophan
residues on the surface of the globule. It is shown that electrostatic interaction of the oppositely charged
groups of BSA and gelatin is responsible for formation of such complex particles, whereas the secondary forces (hydrophobic interaction and hydrogen bonds) play an important role in stabilization of
the complex particles. The zeta potentials of the native and the thermally aggregated BSA samples were
determined, and the solvent quality has been quantified by determining the activity of the protein samples in their saturated solutions. It was shown that steric reasons (large size of the thermally aggregated
BSA particles), and uncomplete charge compensation of the positively charged gelatin molecules by
the negatively charged BSA particles are the main factors in determining structure formation, while
the levels of the activity of the native BSA and BSA have a smaller effect on the structure of complex