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Accelerating Reaction Rates of Biomolecules by Using Shear Stress in Artificial Capillary Systems.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Yates, Emma V 
Toprakcioglu, Zenon  ORCID logo  https://orcid.org/0000-0003-1964-8432
Nadendla, Karthik 

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.

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

Keywords

Journal Title

Journal of the American Chemical Society

Conference Name

Journal ISSN

0002-7863

Volume Title

143

Publisher

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)