Effects of shear on proteins in solution
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The effects of “shear” on proteins in solution are described and discussed. Research on this topic covers many decades, beginning with investigations of possible denaturation of enzymes during processing, whilst more recent concerns are how the quality of therapeutic proteins might be affected by shear or shear related effects. The paradigm that emerges from most studies is that shear in the fluid mechanical sense is unlikely by itself to damage most proteins and that interfacial phenomena are critically important. In particular, moving gas–liquid interfaces can be very deleterious. Aggregation of therapeutic proteins on nanoparticles shed from solid surfaces is a recent concern because of potential consequences on patient safety. It is clear that labeling such damage as “shear” is a mistake as this inhibits clear investigations of, and thinking about, the true causes of damage to proteins in solution during processing.
KeywordsAggregates Enzymes Human therapeutics Interfaces Proteins Shear
The authors sincerely thank Lindsay Schmiedel for critical review and insightful comments and the Formulation Development Group at Merck & Co., Inc. for their support of the manuscript.
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