When: 18 December, 2024, 15:30 - 16:30
Speaker: Amy Xu, Louisiana State University, USA
Title: Characterizing Interactions and Conformational Flexibility of Monoclonal Antibodies Using Small-Angle Scattering
Abstract
Monoclonal antibodies (mAbs) are a major class of biotherapeutics with a wide range of clinical applications. Characterizing the conformation and intermolecular interactions of mAbs in concentrated formulations is crucial for understanding their physical stability and viscosity. Small-angle scattering (SAS) is an ideal method for studying concentrated protein samples with high excipient concentrations. Our previous work used SAS to investigate the stability and viscosity of concentrated NISTmAb formulations under varying pH, salt, and cosolute conditions. In a recent study, we further explored the conformational flexibility and protein-protein interactions (PPI) of NISTmAb under near-neutral and acidic conditions using small-angle X-ray scattering (SAXS) and complementary biophysical methods. We demonstrate that the preferred configurations of mAbs in concentrated formulations can be elucidated from scattering data through the integration of molecular simulations. Our findings indicate that the conformational flexibility of NISTmAb changes significantly with solution pH and that domain-domain interactions play a significant role in determining the overall PPI among the full antibody molecules.
Bio
Dr. Amy Xu completed her Ph.D. in Chemistry from the University of Auckland, New Zealand. During her doctoral research, she investigated how proteins and polysaccharides interacted with each other during a liquid-liquid phase separation process known as complex coacervation, using mainly small-angle X-ray and neutron scattering (SAXS/SANS) techniques. Upon completing her Ph.D. in 2016, Dr. Xu relocated to the US to undertake her first postdoctoral position at the University of Massachusetts Amherst, where she investigated the relationship between molecular structures and preparation conditions to the phase behavior and rheological properties of colloid-polymer complexes. From 2017 to 2020, she pursued her second postdoctoral training at the NIST Center for Neutron Research (NCNR) in Maryland. Her work at NIST centered on advancing small-angle scattering techniques to study the conformation and stability of monoclonal antibodies in concentrated formulations. She joined LSU in August 2020 as an Assistant Professor in Chemistry. Dr. Xu's research at LSU primarily aims to achieve a comprehensive understanding on how biomacromolecules behave and interact in confined environments, from complex coacervates to concentrated protein formulations, using biophysical characterization methods, especially SAXS and SANS.
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