Dynamic interfaces are privileged places for protein adsorption and aggregation
Therapeutic protein solutions are in contact with different materials and air during their storage, preparation and administration. Proteins adsorb onto these solid and gaseous interfaces. Agitation creates dynamic interfaces as the meniscus of the protein solution sweeps across the walls of the container. In this case, the proteins adsorbed on the surface of the container are alternately exposed to air and solution, which results in their partial dehydration.
Using hydrophobic rods soaked in a stirred protein solution, we have demonstrated by fluorescence the privileged and rapid deposition of protein aggregates at the triple point on the rod, where the protein solution, the rod surface and the air meet. This work highlights multiple effects of agitation of a protein solution exposed to interfaces: beyond phenomena sensitive to the mixing of molecules in solution, agitation generates a repeated exposure of adsorbed proteins to air and promotes their aggregation. This mechanism has direct implications on the necessary precautions in the handling protocols of formulations containing therapeutic proteins in order to guarantee their stability, a subject which is at the heart of our collaborations with Sanofi and Becton Dickinson.