posted on 2021-10-04, 20:16authored byTuuli
A. Hakala, Emma V. Yates, Pavan K. Challa, Zenon Toprakcioglu, Karthik Nadendla, Dijana Matak-Vinkovic, Christopher M. Dobson, Rodrigo Martínez, Francisco Corzana, Tuomas P. J. Knowles, Gonçalo J. L. Bernardes
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.