An Investigation of Protein Interactions and the Relationship to Phase Behavior

Protein interactions in solution are inherently linked to phase behavior. A fundamental understanding of the relationship is necessary to develop efficient methods for crystallizing proteins. In this investigation, lysozyme second virial coefficient measurements consistently reflect trends in lysozyme solubility with various solution variables. The measurements demonstrate increased repulsive interactions correspond to greater solubility while increased attractions correspond to reduced solubility. Also, lysozyme second virial coefficient measurements at solution conditions where repulsive interactions dominate are well described by the DLVO interaction potential. Since protein solutions exhibit phase behavior analogous to molecular systems, simple interaction models can be used to describe protein interactions. The adhesive hard sphere model demonstrates protein interactions at crystallization conditions are short range. However, the adhesive hard sphere model provides an incomplete description of protein interactions. Further analysis suggests the attractive Yukawa model provides a more complete description of protein interactions. The attractive Yukawa model incorporates a variable range of attraction that influences the location of phase boundaries. Lysozyme second virial coefficient measurements at critical point conditions in various salt solutions suggest that precipitant identity affects the range of attraction. The model demonstrates that the influence of precipitant identity on the range of attraction has important implications for protein crystallization. This investigation provides further evidence that second virial coefficient measurements are useful for determining solution conditions favorable for protein crystallization.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Rosenbaum, Darren Fredrick

Contributors dc:contributor

• Zukoski, Charles F.

• Engineering, Materials Science

Language dc:language

eng

Identifier

(MiAaPQ)AAI9904573

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82454