Thermodynamic instability and off-critical slowing down in supersaturated lysozyme solutions

Experimental determination of stability conditions or instability boundaries in protein solution is a powerful tool for testing interaction models and for use in seeking an understanding of the mechanisms leading to protein aggregation. In a recent work on lysozyme solutions at different NaCl concentrations, we have determined the instability boundaries (spinodal line) of a liquid-liquid phase separation, metastable with respect to crystallization. Here, we review previous results, pointing out the scaling critical behaviour of isothermal compressibility with respect to spinodal temperatures, and discuss interaction models and the addition of an entropie term. The measured slowing down of concentration fluctuation dynamics is clearly related to the divergence of the fluctuation correlation length on approaching each point of the spinodal line. This observed off-critical slowing down calls for a crucial role for enhanced fluctuations in the crystallization process.