Equilibrium and dynamic design principles for binding molecules engineered for reagentless biosensors
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Griffith_Equilibrium and.pdf
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Author(s)
De Picciotto, Seymour
Imperiali, Barbara
Griffith, Linda G
Wittrup, Karl Dane
Date Issued
May 2014
Journal
Analytical Biochemistry
Publisher
Elsevier
Citation
de Picciotto, Seymour et al. “Equilibrium and Dynamic Design Principles for Binding Molecules Engineered for Reagentless Biosensors.” Analytical Biochemistry 460 (2014): 9–15.
Version
Author's final manuscript
Abstract
Reagentless biosensors rely on the interaction of a binding partner and its target to generate a change in fluorescent signal using an environment-sensitive fluorophore or Förster resonance energy transfer. Binding affinity can exert a significant influence on both the equilibrium and the dynamic response characteristics of such a biosensor. We here develop a kinetic model for the dynamic performance of a reagentless biosensor. Using a sinusoidal signal for ligand concentration, our findings suggest that it is optimal to use a binding moiety whose equilibrium dissociation constant matches that of the average predicted input signal, while maximizing both the association rate constant and the dissociation rate constant at the necessary ratio to create the desired equilibrium constant. Although practical limitations constrain the attainment of these objectives, the derivation of these design principles provides guidance for improved reagentless biosensor performance and metrics for quality standards in the development of biosensors. These concepts are broadly relevant to reagentless biosensor modalities.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.ab.2014.04.036
