ANR-Immunoglobulin

Statische und dynamische Eigenschaften von Antikörperproteinlösungen - Einfluss von Crowding und Ladungen

18/10/2016 to 17/10/2019

The efficient medical dosage of antibodies requires high
concentrations in aqueous solutions. These solutions can in addition contain other molecules, denoted crowding agents, which help to increase the maximum protein concentration or circumvent protein
aggregation. We propose to study both static and dynamic properties of highly concentrated aqueous antibody solutions using small-angle scattering, neutron spectroscopy, and complementary techniques. In
particular, we address the effects of macromolecular crowding and ion-induced charges on the effective protein-protein interactions, phase behavior, and global as well as internal dynamics of antibodies
in solution. We also focus on the dynamic, transient, or static cluster phases in this system depending on the employed physical parameters. The systematic investigation will cover both the effect of
self-crowding by the antibody proteins themselves as well as by external crowding agents such as other proteins (e.g. BSA), polymers (e.g. PEG), and sugars (e.g. trehalose). With view at the peculiar
three-lobed conformation of immunoglobulin antibody proteins, the project will in particular be guided by the role and importance of the protein shape in the determination of the static and dynamic
properties of the protein solutions. Whilst addressing questions related to biophysics and biomedicine, we will employ both experimental and theoretical concepts and methods from soft-matter physics. These methods provide a unique access to molecular length scales and to picosecond to nanosecond time scales of molecular
motions. Our proposed study addresses important questions regarding applied protein science as well as fundamental mechanisms of crowding in solutions of anisotropic particles.