Effective rate models for receptors distributed in a layer above a surface: application to cells and Biacore

Biophysical Journal
C Wofsy, Byron Goldstein

Abstract

In the Biacore biosensor, a widely used tool for studying the kinetics of ligand/receptor binding, receptors are commonly localized to the sensor surface through attachment to polymers that extend from the surface to form a layer. The importance of the polymeric layer in analyzing data is controversial. The question of the effect of a binding layer also arises in the case of ligands interacting with binding sites distributed in the extracellular matrix of cells. To identify and quantify the effects of a binding layer on the estimation of association and dissociation rate constants, we derived effective rate coefficients. The expressions show that rate constants determined under the standard assumption that binding takes place on a two-dimensional surface underestimate the true reaction rate constants by a factor that depends on the ratio of the height of the layer to the mean free path of the ligand within the layer. We show that, for typical biological ligands, receptors, cells, and Biacore conditions, the binding layer will affect the interpretation of data only if transport of the ligand in the layer is slowed substantially--by one or two orders of magnitude--relative to transport outside the layer. From existing experiments...Continue Reading

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Citations

Jun 24, 2006·Bulletin of Mathematical Biology·David A Edwards
Apr 12, 2015·Biophysical Journal·Lining JuCheng Zhu
Mar 17, 2007·The Journal of Chemical Physics·C B Korn, U S Schwarz
Jan 26, 2007·The Journal of Chemical Physics·Ambarish NagAaron R Dinner
Jan 21, 2004·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Sep 22, 2005·Lab on a Chip·Andrea LionelloHubert H Girault
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Jun 4, 2008·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·C B Korn, U S Schwarz
Nov 2, 2004·Analytical Chemistry·Menake E PiyasenaGabriel P Lopez
Aug 14, 2012·Langmuir : the ACS Journal of Surfaces and Colloids·Nicola E Cant, Sarah E Harrison
Jul 28, 2004·Langmuir : the ACS Journal of Surfaces and Colloids·Sonny S MarkCarl A Batt

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