Steric effects on multivalent ligand-receptor binding

Exclusion of ligand sites by bound cell surface receptors

William S. Hlavacek, Richard G Posner, Alan S. Perelson

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Steric effects can influence the binding of a cell surface receptor to a multivalent ligand. To account for steric effects arising from the size of a receptor and from the spacing of binding sites on a ligand, we extend a standard mathematical model for ligand-receptor interactions by introducing a steric hindrance factor. This factor gives the fraction of unbound ligand sites that are accessible to receptors, and thus available for binding, as a function of ligand site occupancy. We derive expressions for the steric hindrance factor for various cases in which the receptor covers a compact region on the ligand surface and the ligand expresses sites that are distributed regularly or randomly in one or two dimensions. These expressions are relevant for ligands such as linear polymers, proteins, and viruses. We also present numerical algorithms that can be used to calculate steric hindrance factors for other cases. These theoretical results allow us to quantify the effects of steric hindrance on ligand-receptor kinetics and equilibria.

Original languageEnglish (US)
Pages (from-to)3031-3043
Number of pages13
JournalBiophysical Journal
Volume76
Issue number6
StatePublished - Jun 1999

Fingerprint

Cell Surface Receptors
Ligands
Polymers
Theoretical Models
Binding Sites
Viruses

ASJC Scopus subject areas

  • Biophysics

Cite this

Steric effects on multivalent ligand-receptor binding : Exclusion of ligand sites by bound cell surface receptors. / Hlavacek, William S.; Posner, Richard G; Perelson, Alan S.

In: Biophysical Journal, Vol. 76, No. 6, 06.1999, p. 3031-3043.

Research output: Contribution to journalArticle

@article{47cab4aed91e43e3b1d80e8056bbbf5c,
title = "Steric effects on multivalent ligand-receptor binding: Exclusion of ligand sites by bound cell surface receptors",
abstract = "Steric effects can influence the binding of a cell surface receptor to a multivalent ligand. To account for steric effects arising from the size of a receptor and from the spacing of binding sites on a ligand, we extend a standard mathematical model for ligand-receptor interactions by introducing a steric hindrance factor. This factor gives the fraction of unbound ligand sites that are accessible to receptors, and thus available for binding, as a function of ligand site occupancy. We derive expressions for the steric hindrance factor for various cases in which the receptor covers a compact region on the ligand surface and the ligand expresses sites that are distributed regularly or randomly in one or two dimensions. These expressions are relevant for ligands such as linear polymers, proteins, and viruses. We also present numerical algorithms that can be used to calculate steric hindrance factors for other cases. These theoretical results allow us to quantify the effects of steric hindrance on ligand-receptor kinetics and equilibria.",
author = "Hlavacek, {William S.} and Posner, {Richard G} and Perelson, {Alan S.}",
year = "1999",
month = "6",
language = "English (US)",
volume = "76",
pages = "3031--3043",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "6",

}

TY - JOUR

T1 - Steric effects on multivalent ligand-receptor binding

T2 - Exclusion of ligand sites by bound cell surface receptors

AU - Hlavacek, William S.

AU - Posner, Richard G

AU - Perelson, Alan S.

PY - 1999/6

Y1 - 1999/6

N2 - Steric effects can influence the binding of a cell surface receptor to a multivalent ligand. To account for steric effects arising from the size of a receptor and from the spacing of binding sites on a ligand, we extend a standard mathematical model for ligand-receptor interactions by introducing a steric hindrance factor. This factor gives the fraction of unbound ligand sites that are accessible to receptors, and thus available for binding, as a function of ligand site occupancy. We derive expressions for the steric hindrance factor for various cases in which the receptor covers a compact region on the ligand surface and the ligand expresses sites that are distributed regularly or randomly in one or two dimensions. These expressions are relevant for ligands such as linear polymers, proteins, and viruses. We also present numerical algorithms that can be used to calculate steric hindrance factors for other cases. These theoretical results allow us to quantify the effects of steric hindrance on ligand-receptor kinetics and equilibria.

AB - Steric effects can influence the binding of a cell surface receptor to a multivalent ligand. To account for steric effects arising from the size of a receptor and from the spacing of binding sites on a ligand, we extend a standard mathematical model for ligand-receptor interactions by introducing a steric hindrance factor. This factor gives the fraction of unbound ligand sites that are accessible to receptors, and thus available for binding, as a function of ligand site occupancy. We derive expressions for the steric hindrance factor for various cases in which the receptor covers a compact region on the ligand surface and the ligand expresses sites that are distributed regularly or randomly in one or two dimensions. These expressions are relevant for ligands such as linear polymers, proteins, and viruses. We also present numerical algorithms that can be used to calculate steric hindrance factors for other cases. These theoretical results allow us to quantify the effects of steric hindrance on ligand-receptor kinetics and equilibria.

UR - http://www.scopus.com/inward/record.url?scp=0033002586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033002586&partnerID=8YFLogxK

M3 - Article

VL - 76

SP - 3031

EP - 3043

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 6

ER -