@article{Plesa:2023:10.1007/s10910-023-01495-3,
author = {Plesa, T and Dack, A and Ouldridge, T},
doi = {10.1007/s10910-023-01495-3},
journal = {Journal of Mathematical Chemistry},
pages = {1980--2018},
title = {Integral feedback in synthetic biology: negative-equilibrium catastrophe},
url = {http://dx.doi.org/10.1007/s10910-023-01495-3},
volume = {61},
year = {2023}
}

Download

TY  - JOUR
AB  - A central goal of synthetic biology is the design of molecular controllers that can manipulate the dynamics of intracellular networks in a stable and accurate manner. To address the factthat detailed knowledge about intracellular networks is unavailable, integral-feedback controllers(IFCs) have been put forward for controlling molecular abundances. These controllers can maintainaccuracy in spite of the uncertainties in the controlled networks. However, this desirable feature isachieved only if stability is also maintained. In this paper, we show that molecular IFCs can sufferfrom a hazardous instability called negative-equilibrium catastrophe (NEC), whereby all nonnegative equilibria vanish under the action of the controllers, and some of the molecular abundancesblow up. We show that unimolecular IFCs do not exist due to a NEC. We then derive a familyof bimolecular IFCs that are safeguarded against NECs when uncertain unimolecular networks,with any number of molecular species, are controlled. However, when IFCs are applied on uncertain bimolecular (and hence most intracellular) networks, we show that preventing NECs generallybecomes an intractable problem as the number of interacting molecular species increases. NECstherefore place a fundamental limit to design and control of molecular networks.
AU  - Plesa,T
AU  - Dack,A
AU  - Ouldridge,T
DO  - 10.1007/s10910-023-01495-3
EP  - 2018
PY  - 2023///
SN  - 0259-9791
SP  - 1980
TI  - Integral feedback in synthetic biology: negative-equilibrium catastrophe
T2  - Journal of Mathematical Chemistry
UR  - http://dx.doi.org/10.1007/s10910-023-01495-3
UR  - https://link.springer.com/article/10.1007/s10910-023-01495-3
UR  - http://hdl.handle.net/10044/1/105397
VL  - 61
ER  - 

Download