NDLI: Phase transitions in human IgG solutions

Content Provider	PubMed Central
Author	Wang, Ying Lomakin, Aleksey Latypov, Ramil F. Laubach, Jacob P. Hideshima, Teru Richardson, Paul G. Munshi, Nikhil C. Anderson, Kenneth C. Benedek, George B.
Copyright Year	2013
Abstract	Protein condensations, such as crystallization, liquid-liquid phase separation, aggregation, and gelation, have been observed in concentrated antibody solutions under various solution conditions. While most IgG antibodies are quite soluble, a few outliers can undergo condensation under physiological conditions. Condensation of IgGs can cause serious consequences in some human diseases and in biopharmaceutical formulations. The phase transitions underlying protein condensations in concentrated IgG solutions is also of fundamental interest for the understanding of the phase behavior of non-spherical protein molecules. Due to the high solubility of generic IgGs, the phase behavior of IgG solutions has not yet been well studied. In this work, we present an experimental approach to study IgG solutions in which the phase transitions are hidden below the freezing point of the solution. Using this method, we have investigated liquid-liquid phase separation of six human myeloma IgGs and two recombinant pharmaceutical human IgGs. We have also studied the relation between crystallization and liquid-liquid phase separation of two human cryoglobulin IgGs. Our experimental results reveal several important features of the generic phase behavior of IgG solutions: (1) the shape of the coexistence curve is similar for all IgGs but quite different from that of quasi-spherical proteins; (2) all IgGs have critical points located at roughly the same protein concentration at ∼100 mg/ml while their critical temperatures vary significantly; and (3) the liquid-liquid phase separation in IgG solutions is metastable with respect to crystallization. These features of phase behavior of IgG solutions reflect the fact that all IgGs have nearly identical molecular geometry but quite diverse net inter-protein interaction energies. This work provides a foundation for further experimental and theoretical studies of the phase behavior of generic IgGs as well as outliers with large propensity to condense. The investigation of the phase diagram of IgG solutions is of great importance for the understanding of immunoglobulin deposition diseases as well as for the understanding of the colloidal stability of IgG pharmaceutical formulations.
Related Links	http://dx.doi.org/10.1063/1.4811345
Starting Page	121904
File Format	PDF
ISSN	10897690
e-ISSN	10897690
Journal	The Journal of Chemical Physics
Issue Number	12
Volume Number	139
Language	English
Publisher	American Institute of Physics
Publisher Date	2013-09-28
Access Restriction	Open
Rights Holder	American Institute of Physics
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physics and Astronomy Medicine Physical and Theoretical Chemistry

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