Accelerating Reaction Rates of Biomolecules by Using Shear Stress in Artificial Capillary Systems.
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Authors
Yates, Emma V
Nadendla, Karthik
Matak-Vinkovic, Dijana
Dobson, Christopher M
Publication Date
2021-10-04Journal Title
Journal of the American Chemical Society
ISSN
0002-7863
Volume
143
Issue
40
Pages
16401-16410
Language
eng
Type
Article
This Version
VoR
Metadata
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Hakala, T. A., Yates, E. V., Challa, P. K., Toprakcioglu, Z., Nadendla, K., Matak-Vinkovic, D., Dobson, C. M., et al. (2021). Accelerating Reaction Rates of Biomolecules by Using Shear Stress in Artificial Capillary Systems.. Journal of the American Chemical Society, 143 (40), 16401-16410. https://doi.org/10.1021/jacs.1c03681
Description
Funder: Frances and Augustus Newman Foundation
Funder: Emmanuel College, University of Cambridge
Funder: Biotechnology and Biological Sciences Research Council
Funder: Centre for Misfolding Diseases, University of Cambridge
Funder: Wellcome Trust
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.
Sponsorship
H2020 Marie Sk??odowska-Curie Actions (67500)
Royal Society (URF80019)
European Research Council (337969)
Agencia Estatal de Investigaci??n, Ministerio de Ciencia, Innovaci??n y Universidades (RTI2018-099592-B-C21, PGC2018-098561-B)
Funda????o para a Ci??ncia e a Tecnologia (CEECIND/00453/2018)
Identifiers
PMC8517977, 34606279
External DOI: https://doi.org/10.1021/jacs.1c03681
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330321
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