Accelerating Reaction Rates of Biomolecules by Using Shear Stress in Artificial Capillary Systems
Tuuli A. Hakala, Emma V. Yates, Pavan K. Challa, Zenon Toprakcioglu, Karthik Nadendla, Dijana Matak‐Vinković, Christopher M. Dobson, Rodrigo Martı́nez, Francisco Corzana, Tuomas P. J. Knowles, Gonçalo J. L. Bernardes
Abstract
Biomimetics is a design principle within chemistry, biology, and engineering, but chemistry biomimetic approaches have been generally limited to emulating nature's chemical toolkit while emulation of nature's physical toolkit has remained largely unexplored. To begin to explore this, we designed biophysically mimetic microfluidic reactors with characteristic length scales and shear stresses observed within capillaries. We modeled the effect of shear with molecular dynamics studies and showed that this induces specific normally buried residues to become solvent accessible. We then showed using kinetics experiments that rates of reaction of these specific residues in fact increase in a shear-dependent fashion. We applied our results in the creation of a new microfluidic approach for the multidimensional study of cysteine biomarkers. Finally, we used our approach to establish dissociation of the therapeutic antibody trastuzumab in a reducing environment. Our results have implications for the efficacy of existing therapeutic antibodies in blood plasma as well as suggesting in general that biophysically mimetic chemistry is exploited in biology and should be explored as a research area.