Adsorption-desorption dynamics at the solid-liquid interface govern monoclonal antibody aggregation under mechanical stress: Roles of Hofmeister anions and vial surface hydrophobicity.

Antibody formulations are routinely exposed to air-liquid and solid-liquid interfaces during manufacturing, transportation, and drug administration, yet formulation design still relies mainly on bulk-phase stability parameters, which poorly predict aggregation under interfacial stress. Here we combined interfacial experiments and dissipative particle dynamics (DPD) simulations to dissect how Hofmeister-series salts and container-wall hydrophobicity jointly govern the stability of two monoclonal antibodies (mAb-1 and mAb-2) under mechanical stress. When bulk-phase stability was comparable, hydrophobizing the vial surface by octyltriethoxysilane silanization suppressed the growth of insoluble subvisible particles in mAb-1 by promoting stable protein layer adsorption. DPD simulations resolved the molecular basis of this stabilization: mAb-1 formed a flat, immobilized monomolecular protective layer at the solid-liquid interface (sliding-transition frequency 0.7), whereas mAb-2 underwent frequent adsorption-desorption cycles (transition frequency 3.6) that released denatured monomers back into the bulk and caused protein aggregation. Beyond bulk electrostatic effects, Hofmeister anions reshaped the interfacial hydration environment and thereby tuned how much protein adsorbed, how strongly it was retained, and how often it desorbed, kosmotropic sulfate enriched protein at interfaces through preferential exclusion, chaotropic thiocyanate strengthened retention at hydrophobic surfaces. Interfacial experiments and DPD simulations together show that profiling antibody adsorption dynamics across surfaces and Hofmeister salts identifies stabilizing combinations that bulk-phase stability metrics alone cannot predict, offering a practical strategy for formulation and packaging design.