Cargando…

Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions

Integrin adhesome proteins bind each other in alternative manners, forming within the cell diverse cell-matrix adhesion sites with distinct properties. An intriguing question is how such modular assembly of adhesion sites is achieved correctly solely by self-organization of their components. Here we...

Descripción completa

Detalles Bibliográficos
Autores principales: Harizanova, Jana, Fermin, Yessica, Malik-Sheriff, Rahuman S., Wieczorek, Jakob, Ickstadt, Katja, Grecco, Hernán E., Zamir, Eli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982658/
https://www.ncbi.nlm.nih.gov/pubmed/27519053
http://dx.doi.org/10.1371/journal.pone.0160591
_version_ 1782447811493625856
author Harizanova, Jana
Fermin, Yessica
Malik-Sheriff, Rahuman S.
Wieczorek, Jakob
Ickstadt, Katja
Grecco, Hernán E.
Zamir, Eli
author_facet Harizanova, Jana
Fermin, Yessica
Malik-Sheriff, Rahuman S.
Wieczorek, Jakob
Ickstadt, Katja
Grecco, Hernán E.
Zamir, Eli
author_sort Harizanova, Jana
collection PubMed
description Integrin adhesome proteins bind each other in alternative manners, forming within the cell diverse cell-matrix adhesion sites with distinct properties. An intriguing question is how such modular assembly of adhesion sites is achieved correctly solely by self-organization of their components. Here we address this question using high-throughput multiplexed imaging of eight proteins and two phosphorylation sites in a large number of single focal adhesions. We found that during the assembly of focal adhesions the variances of protein densities decrease while the correlations between them increase, suggesting reduction in the noise levels within these structures. These changes correlate independently with the area and internal density of focal adhesions, but not with their age or shape. Artificial neural network analysis indicates that a joint consideration of multiple components improves the predictability of paxillin and zyxin levels in internally dense focal adhesions. This suggests that paxillin and zyxin densities in focal adhesions are fine-tuned by integrating the levels of multiple other components, thus averaging-out stochastic fluctuations. Based on these results we propose that increase in internal protein densities facilitates noise suppression in focal adhesions, while noise suppression enables their stable growth and further density increase—hence forming a feedback loop giving rise to a quality-controlled assembly.
format Online
Article
Text
id pubmed-4982658
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-49826582016-08-29 Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions Harizanova, Jana Fermin, Yessica Malik-Sheriff, Rahuman S. Wieczorek, Jakob Ickstadt, Katja Grecco, Hernán E. Zamir, Eli PLoS One Research Article Integrin adhesome proteins bind each other in alternative manners, forming within the cell diverse cell-matrix adhesion sites with distinct properties. An intriguing question is how such modular assembly of adhesion sites is achieved correctly solely by self-organization of their components. Here we address this question using high-throughput multiplexed imaging of eight proteins and two phosphorylation sites in a large number of single focal adhesions. We found that during the assembly of focal adhesions the variances of protein densities decrease while the correlations between them increase, suggesting reduction in the noise levels within these structures. These changes correlate independently with the area and internal density of focal adhesions, but not with their age or shape. Artificial neural network analysis indicates that a joint consideration of multiple components improves the predictability of paxillin and zyxin levels in internally dense focal adhesions. This suggests that paxillin and zyxin densities in focal adhesions are fine-tuned by integrating the levels of multiple other components, thus averaging-out stochastic fluctuations. Based on these results we propose that increase in internal protein densities facilitates noise suppression in focal adhesions, while noise suppression enables their stable growth and further density increase—hence forming a feedback loop giving rise to a quality-controlled assembly. Public Library of Science 2016-08-12 /pmc/articles/PMC4982658/ /pubmed/27519053 http://dx.doi.org/10.1371/journal.pone.0160591 Text en © 2016 Harizanova et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Harizanova, Jana
Fermin, Yessica
Malik-Sheriff, Rahuman S.
Wieczorek, Jakob
Ickstadt, Katja
Grecco, Hernán E.
Zamir, Eli
Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions
title Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions
title_full Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions
title_fullStr Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions
title_full_unstemmed Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions
title_short Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions
title_sort highly multiplexed imaging uncovers changes in compositional noise within assembling focal adhesions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982658/
https://www.ncbi.nlm.nih.gov/pubmed/27519053
http://dx.doi.org/10.1371/journal.pone.0160591
work_keys_str_mv AT harizanovajana highlymultiplexedimaginguncoverschangesincompositionalnoisewithinassemblingfocaladhesions
AT ferminyessica highlymultiplexedimaginguncoverschangesincompositionalnoisewithinassemblingfocaladhesions
AT maliksheriffrahumans highlymultiplexedimaginguncoverschangesincompositionalnoisewithinassemblingfocaladhesions
AT wieczorekjakob highlymultiplexedimaginguncoverschangesincompositionalnoisewithinassemblingfocaladhesions
AT ickstadtkatja highlymultiplexedimaginguncoverschangesincompositionalnoisewithinassemblingfocaladhesions
AT greccohernane highlymultiplexedimaginguncoverschangesincompositionalnoisewithinassemblingfocaladhesions
AT zamireli highlymultiplexedimaginguncoverschangesincompositionalnoisewithinassemblingfocaladhesions