Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.

Immune synapses formed by T and NK cells both show segregation of the integrin ICAM1 from other proteins such as CD2 (T cell) or KIR (NK cell). However, the mechanism by which these proteins segregate remains unclear; one key hypothesis is a redistribution based on protein size. Simulations of this...

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Autores principales:	Nigel J Burroughs, Karsten Köhler, Vladimir Miloserdov, Michael L Dustin, P Anton van der Merwe, Daniel M Davis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/80a802b1b7a9445c8d033501939a678f
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spelling	oai:doaj.org-article:80a802b1b7a9445c8d033501939a678f2021-11-18T05:50:23ZBoltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.1553-734X1553-735810.1371/journal.pcbi.1002076https://doaj.org/article/80a802b1b7a9445c8d033501939a678f2011-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829338/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Immune synapses formed by T and NK cells both show segregation of the integrin ICAM1 from other proteins such as CD2 (T cell) or KIR (NK cell). However, the mechanism by which these proteins segregate remains unclear; one key hypothesis is a redistribution based on protein size. Simulations of this mechanism qualitatively reproduce observed segregation patterns, but only in certain parameter regimes. Verifying that these parameter constraints in fact hold has not been possible to date, this requiring a quantitative coupling of theory to experimental data. Here, we address this challenge, developing a new methodology for analysing and quantifying image data and its integration with biophysical models. Specifically we fit a binding kinetics model to 2 colour fluorescence data for cytoskeleton independent synapses (2 and 3D) and test whether the observed inverse correlation between fluorophores conforms to size dependent exclusion, and further, whether patterned states are predicted when model parameters are estimated on individual synapses. All synapses analysed satisfy these conditions demonstrating that the mechanisms of protein redistribution have identifiable signatures in their spatial patterns. We conclude that energy processes implicit in protein size based segregation can drive the patternation observed in individual synapses, at least for the specific examples tested, such that no additional processes need to be invoked. This implies that biophysical processes within the membrane interface have a crucial impact on cell:cell communication and cell signalling, governing protein interactions and protein aggregation.Nigel J BurroughsKarsten KöhlerVladimir MiloserdovMichael L DustinP Anton van der MerweDaniel M DavisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 8, p e1002076 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Nigel J Burroughs Karsten Köhler Vladimir Miloserdov Michael L Dustin P Anton van der Merwe Daniel M Davis Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.
description	Immune synapses formed by T and NK cells both show segregation of the integrin ICAM1 from other proteins such as CD2 (T cell) or KIR (NK cell). However, the mechanism by which these proteins segregate remains unclear; one key hypothesis is a redistribution based on protein size. Simulations of this mechanism qualitatively reproduce observed segregation patterns, but only in certain parameter regimes. Verifying that these parameter constraints in fact hold has not been possible to date, this requiring a quantitative coupling of theory to experimental data. Here, we address this challenge, developing a new methodology for analysing and quantifying image data and its integration with biophysical models. Specifically we fit a binding kinetics model to 2 colour fluorescence data for cytoskeleton independent synapses (2 and 3D) and test whether the observed inverse correlation between fluorophores conforms to size dependent exclusion, and further, whether patterned states are predicted when model parameters are estimated on individual synapses. All synapses analysed satisfy these conditions demonstrating that the mechanisms of protein redistribution have identifiable signatures in their spatial patterns. We conclude that energy processes implicit in protein size based segregation can drive the patternation observed in individual synapses, at least for the specific examples tested, such that no additional processes need to be invoked. This implies that biophysical processes within the membrane interface have a crucial impact on cell:cell communication and cell signalling, governing protein interactions and protein aggregation.
format	article
author	Nigel J Burroughs Karsten Köhler Vladimir Miloserdov Michael L Dustin P Anton van der Merwe Daniel M Davis
author_facet	Nigel J Burroughs Karsten Köhler Vladimir Miloserdov Michael L Dustin P Anton van der Merwe Daniel M Davis
author_sort	Nigel J Burroughs
title	Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.
title_short	Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.
title_full	Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.
title_fullStr	Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.
title_full_unstemmed	Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.
title_sort	boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/80a802b1b7a9445c8d033501939a678f
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Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses.

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