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Phase transitions in protein solutions

Wednesday 23rd June 2004 - 10:00 to 11:00
INI Seminar Room 1
Session Title: 
Protein-Protein Interactions in Vitro and in Vivo

Dense liquid, gel-like and solid, ordered in three, two, or one dimension, or completely disordered phases form in protein solutions and underlie physiological and patho-physiological, laboratory, and technological processes. The loss of phase stability of the protein solution represents the ultimate form of intermolecular interactions at high solution concentrations. The loss of phase stability can be accompanied by loss of conformational stability, as in the formation of the amyloid fibrils, or occur with preservation of the protein conformation.

Two aspects of the phase transitions will be discussed.

The first one is the role of water, structured at the hydrophobic and hydrophilic patches on the surface of the protein molecules. Examples will be provided illustrating that this structuring often determines the entropy and enthalpy balance of the phase transition, leads to unusual intermolecular interaction potentials with one or more outlying maxima, which severely affect the phase diagrams, and that the dynamics of destruction of the water shell is the major determinant of the kinetics of association of molecules into solid phases. Because of the water structuring, the fastest pathway of nucleation of ordered solid phases is not the one with the lowest free-energy barriers.

The second aspect is the interaction between the phases. Examples from the nucleation of two types of ordered solid phases: three-dimensional crystals and the polymers of sickle cell hemoglobin, which have one-dimensional translational symmetry, show that nucleation proceeds via a disordered liquid-like intermediate. In crystal nucleation, the structuring of the intermediate is the rate determining step in the nucleation process, while in the nucleation of the HbS polymers, the formation of the intermediate determines the overall nucleation rate.

Phys. Rev. Lett. 84, 1339 (2000); Nature 406, 494 (2000); Proc. Natl. Acad. Sci. USA 97, 6277 (2000); Solid State Physics 57, 1 (2002); Proc. Natl. Acad. Sci. USA 100, 792 (2003); Methods in Enzymology 368, 84 (2003); Biophys. J. 85, 3935 (2003); J. Am. Chem. Soc. 125, 11684 (2003); J. Mol. Biol. 336, 43–59 (2004); Crystal Growth and Design 5, in print (2004).

University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons