Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.

Cell adhesion is mediated by numerous membrane receptors. It is desirable to derive the outcome of a cell-surface encounter from the molecular properties of interacting receptors and ligands. However, conventional parameters such as affinity or kinetic constants are often insufficient to account for...

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Autores principales:	Valentina Lo Schiavo, Philippe Robert, Laurent Limozin, Pierre Bongrand
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/28bf38d538c846fca512c6f818c9d331
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spelling	oai:doaj.org-article:28bf38d538c846fca512c6f818c9d3312021-11-18T07:05:33ZQuantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.1932-620310.1371/journal.pone.0044070https://doaj.org/article/28bf38d538c846fca512c6f818c9d3312012-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0044070https://doaj.org/toc/1932-6203Cell adhesion is mediated by numerous membrane receptors. It is desirable to derive the outcome of a cell-surface encounter from the molecular properties of interacting receptors and ligands. However, conventional parameters such as affinity or kinetic constants are often insufficient to account for receptor efficiency. Avidity is a qualitative concept frequently used to describe biomolecule interactions: this includes incompletely defined properties such as the capacity to form multivalent attachments. The aim of this study is to produce a working description of monovalent attachments formed by a model system, then to measure and interpret the behavior of divalent attachments under force. We investigated attachments between antibody-coated microspheres and surfaces coated with sparse monomeric or dimeric ligands. When bonds were subjected to a pulling force, they exhibited both a force-dependent dissociation consistent with Bell's empirical formula and a force- and time-dependent strengthening well described by a single parameter. Divalent attachments were stronger and less dependent on forces than monovalent ones. The proportion of divalent attachments resisting a force of 30 piconewtons for at least 5 s was 3.7 fold higher than that of monovalent attachments. Quantitative modeling showed that this required rebinding, i.e. additional bond formation between surfaces linked by divalent receptors forming only one bond. Further, experimental data were compatible with but did not require stress sharing between bonds within divalent attachments. Thus many ligand-receptor interactions do not behave as single-step reactions in the millisecond to second timescale. Rather, they exhibit progressive stabilization. This explains the high efficiency of multimerized or clustered receptors even when bonds are only subjected to moderate forces. Our approach provides a quantitative way of relating binding avidity to measurable parameters including bond maturation, rebinding and force sharing, provided these parameters have been determined. Also, this provides a quantitative description of the phenomenon of bond strengthening.Valentina Lo SchiavoPhilippe RobertLaurent LimozinPierre BongrandPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44070 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valentina Lo Schiavo Philippe Robert Laurent Limozin Pierre Bongrand Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.
description	Cell adhesion is mediated by numerous membrane receptors. It is desirable to derive the outcome of a cell-surface encounter from the molecular properties of interacting receptors and ligands. However, conventional parameters such as affinity or kinetic constants are often insufficient to account for receptor efficiency. Avidity is a qualitative concept frequently used to describe biomolecule interactions: this includes incompletely defined properties such as the capacity to form multivalent attachments. The aim of this study is to produce a working description of monovalent attachments formed by a model system, then to measure and interpret the behavior of divalent attachments under force. We investigated attachments between antibody-coated microspheres and surfaces coated with sparse monomeric or dimeric ligands. When bonds were subjected to a pulling force, they exhibited both a force-dependent dissociation consistent with Bell's empirical formula and a force- and time-dependent strengthening well described by a single parameter. Divalent attachments were stronger and less dependent on forces than monovalent ones. The proportion of divalent attachments resisting a force of 30 piconewtons for at least 5 s was 3.7 fold higher than that of monovalent attachments. Quantitative modeling showed that this required rebinding, i.e. additional bond formation between surfaces linked by divalent receptors forming only one bond. Further, experimental data were compatible with but did not require stress sharing between bonds within divalent attachments. Thus many ligand-receptor interactions do not behave as single-step reactions in the millisecond to second timescale. Rather, they exhibit progressive stabilization. This explains the high efficiency of multimerized or clustered receptors even when bonds are only subjected to moderate forces. Our approach provides a quantitative way of relating binding avidity to measurable parameters including bond maturation, rebinding and force sharing, provided these parameters have been determined. Also, this provides a quantitative description of the phenomenon of bond strengthening.
format	article
author	Valentina Lo Schiavo Philippe Robert Laurent Limozin Pierre Bongrand
author_facet	Valentina Lo Schiavo Philippe Robert Laurent Limozin Pierre Bongrand
author_sort	Valentina Lo Schiavo
title	Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.
title_short	Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.
title_full	Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.
title_fullStr	Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.
title_full_unstemmed	Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.
title_sort	quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/28bf38d538c846fca512c6f818c9d331
work_keys_str_mv	AT valentinaloschiavo quantitativemodelingassessesthecontributionofbondstrengtheningrebindingandforcesharingtotheavidityofbiomoleculeinteractions AT philipperobert quantitativemodelingassessesthecontributionofbondstrengtheningrebindingandforcesharingtotheavidityofbiomoleculeinteractions AT laurentlimozin quantitativemodelingassessesthecontributionofbondstrengtheningrebindingandforcesharingtotheavidityofbiomoleculeinteractions AT pierrebongrand quantitativemodelingassessesthecontributionofbondstrengtheningrebindingandforcesharingtotheavidityofbiomoleculeinteractions
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Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.

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