Correlation between thermal aggregation and stability of lysozyme with salts described by molar surface tension increment: an exceptional propensity of ammonium salts as aggregation suppressor

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Protein aggregation is a critical problem for biotechnology and pharmaceutical industries.Despite the fact that soluble proteins have been used for many applications, our understandingof the effect of the solution chemistry on protein aggregation still remains to be elucidated.This paper investigates the process of thermal aggregation of lysozyme in the presence ofvarious types of salts. The simple law was found; the aggregation rate of lysozyme increasedwith increasing melting temperature of the protein (Tm) governed by chemical characteristicsof additional salts. Ammonium salts were, however, ruled out; the aggregation rates oflysozyme in the presence of the ammonium salts were smaller than the ones estimatedfrom Tm. Comparing with sodium salts, ammonium salts increased the solubility of thehydrophobic amino acids, indicating that ammonium salts adsorb the hydrophobic region ofproteins, which leads to the decrease in aggregation more effectively than sodium salts. Thepositive relation between aggregation rate and Tm was described by another factor such as thesurface tension of salt solutions. Fourier transform infrared spectral analysis showed thatthe thermal aggregates were likely to form b-sheet in solutions that give high molar surfacetension increment. These results suggest that protein aggregation is attributed to the surfacefree energy of the solution.