Inducing protein aggregation by extensional flow

著者: John Dobson, Amit Kumar, Leon F. Willis, Roman Tůma, Daniel R. Higazi, Richard E. Turner, David C. Lowe, Alison E. Ashcroft, Sheena E. Radford, Nikil Kapur, David J. Brockwell - Proceedings of the National Academy of Sciences, PNAS 2017 被引用: 118

Significance Proteins are inherently sensitive to environmental factors that include hydrodynamic flow. Flow-induced protein remodeling is used in vivo and can also trigger the aggregation of therapeutic proteins during manufacture. Currently, the relative importance of shear and extensional hydrodynamic flow fields to aggregation remains unclear. Here we develop a flow device that subjects proteins to a defined and quantified flow field that is dominated by extensional flow. We show that extensional flow is crucial to induce the aggregation of globular proteins and that flow-induced aggregation is dependent on both protein structure and sequence. These observations rationalize the diverse effects of hydrodynamic flow on protein structure and aggregation propensity seen in both Nature and in protein manufacture.