Explaining the non-Newtonian character of aggregating monoclonal antibody solutions using small-angle neutron scattering

Maria Monica Castellanos, Jai A. Pathak, William Leach, Steven M. Bishop, Ralph H. Colby

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18 Scopus citations

Abstract

A monoclonal antibody solution displays an increase in low shear rate viscosity upon aggregation after prolonged incubation at 40°C. The morphology and interactions leading to the formation of the aggregates responsible for this non-Newtonian character are resolved using small-angle neutron scattering. Our data show a weak repulsive barrier before proteins aggregate reversibly, unless a favorable contact with high binding energy occurs. Two types of aggregates were identified after incubation at 40°C: oligomers with radius of gyration ∼10 nm and fractal submicrometer particles formed by a slow reaction-limited aggregation process, consistent with monomers colliding many times before finding a favorable strong interaction site. Before incubation, these antibody solutions are Newtonian liquids with no increase in low shear rate viscosity and no upturn in scattering at low wavevector, whereas aggregated solutions under the same conditions have both of these features. These results demonstrate that fractal submicrometer particles are responsible for the increase in low shear rate viscosity and low wavevector upturn in scattered intensity of aggregated antibody solutions; both are removed from aggregated samples by filtering.

Original languageEnglish (US)
Pages (from-to)469-476
Number of pages8
JournalBiophysical journal
Volume107
Issue number2
DOIs
StatePublished - Jul 15 2014

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All Science Journal Classification (ASJC) codes

  • Biophysics

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