Surface-induced stability change of bioengineered antibodies: Insights from QCM-D and neutron reflection

Ensuring the long-term stability of therapeutic antibodies (mAbs) is essential to maintain their efficacy and safety in biopharmaceutical applications, but surface-induced conformational changes can compromise protein structure and functionality. It is crucial to establish how surfaces in contact with mAbs during production, transport and storage affect their adsorption and related structural changes.

This study investigates the adsorption dynamics and stability of mAbs COE-3 and COE-7 on three widely used material substrates, silicon dioxide (SiO₂), titanium dioxide (TiO₂), and stainless steel (SS). Through Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), Spectroscopic Ellipsometry (SE), and Neutron Reflection (NR), the long-term interfacial behavior of these antibodies is investigated in practical settings.

COE-3 rapidly achieves adsorption equilibrium, forming stable and rigid layers on all surfaces with minimal structural alteration. In contrast, COE-7 initially forms a hydrated and viscoelastic layer on SiO₂ and TiO₂, which undergoes compaction over time, indicating sensitivity to surface-induced conformational changes. On SS, however, both antibodies form compact and stable layers. Raman spectroscopy reveals phenylalanine conformation changes as a key factor in COE-7's collapse on specific surfaces. This study highlights the significant role of surface chemistry in modulating antibody hydration, conformation, and stability and demonstrates the complementary utility of QCM-D, SE, and NR in characterizing antibody-surface interactions.