Imperial College London
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DrVahidShahrezaei

Faculty of Natural Sciences, Department of Mathematics

Reader in Biomathematics
 
 
 
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Contact

 

+44 (0)20 7594 8516v.shahrezaei Website

 
 
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Location

 

301BSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Dushek:2014:10.1016/j.bpj.2014.06.021,
author = {Dushek, O and Lellouch, AC and Vaux, DJ and Shahrezaei, V},
doi = {10.1016/j.bpj.2014.06.021},
journal = {Biophysical Journal},
pages = {773--782},
title = {Biosensor Architectures for High-Fidelity Reporting of Cellular Signaling},
url = {http://dx.doi.org/10.1016/j.bpj.2014.06.021},
volume = {107},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Understanding mechanisms of information processing in cellular signaling networks requires quantitative measurements of protein activities in living cells. Biosensors are molecular probes that have been developed to directly track the activity of specific signaling proteins and their use is revolutionizing our understanding of signal transduction. The use of biosensors relies on the assumption that their activity is linearly proportional to the activity of the signaling protein they have been engineered to track. We use mechanistic mathematical models of common biosensor architectures (single-chain FRET-based biosensors), which include both intramolecular and intermolecular reactions, to study the validity of the linearity assumption. As a result of the classic mechanism of zero-order ultrasensitivity, we find that biosensor activity can be highly nonlinear so that small changes in signaling protein activity can give rise to large changes in biosensor activity and vice versa. This nonlinearity is abolished in architectures that favor the formation of biosensor oligomers, but oligomeric biosensors produce complicated FRET states. Based on this finding, we show that high-fidelity reporting is possible when a single-chain intermolecular biosensor is used that cannot undergo intramolecular reactions and is restricted to forming dimers. We provide phase diagrams that compare various trade-offs, including observer effects, which further highlight the utility of biosensor architectures that favor intermolecular over intramolecular binding. We discuss challenges in calibrating and constructing biosensors and highlight the utility of mathematical models in designing novel probes for cellular signaling.
AU  - Dushek,O
AU  - Lellouch,AC
AU  - Vaux,DJ
AU  - Shahrezaei,V
DO  - 10.1016/j.bpj.2014.06.021
EP  - 782
PY  - 2014///
SN  - 1542-0086
SP  - 773
TI  - Biosensor Architectures for High-Fidelity Reporting of Cellular Signaling
T2  - Biophysical Journal
UR  - http://dx.doi.org/10.1016/j.bpj.2014.06.021
UR  - http://hdl.handle.net/10044/1/26443
VL  - 107
ER  -
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