Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds

Abstract Quantitative approaches to analyze the large data sets generated by single molecule localization super-resolution microscopy (SMLM) are limited. We developed a computational pipeline and applied it to analyzing 3D point clouds of SMLM localizations (event lists) of the caveolar coat protein...

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Autores principales:	Ismail M. Khater, Fanrui Meng, Timothy H. Wong, Ivan Robert Nabi, Ghassan Hamarneh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a27e59028cde44fbb21695413a32161e
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spelling	oai:doaj.org-article:a27e59028cde44fbb21695413a32161e2021-12-02T15:07:47ZSuper Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds10.1038/s41598-018-27216-42045-2322https://doaj.org/article/a27e59028cde44fbb21695413a32161e2018-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-27216-4https://doaj.org/toc/2045-2322Abstract Quantitative approaches to analyze the large data sets generated by single molecule localization super-resolution microscopy (SMLM) are limited. We developed a computational pipeline and applied it to analyzing 3D point clouds of SMLM localizations (event lists) of the caveolar coat protein, caveolin-1 (Cav1), in prostate cancer cells differentially expressing CAVIN1 (also known as PTRF), that is also required for caveolae formation. High degree (strongly-interacting) points were removed by an iterative blink merging algorithm and Cav1 network properties were compared with randomly generated networks to retain a sub-network of geometric structures (or blobs). Machine-learning based classification extracted 28 quantitative features describing the size, shape, topology and network characteristics of ∼80,000 blobs. Unsupervised clustering identified small S1A scaffolds corresponding to SDS-resistant Cav1 oligomers, as yet undescribed larger hemi-spherical S2 scaffolds and, only in CAVIN1-expressing cells, spherical, hollow caveolae. Multi-threshold modularity analysis suggests that S1A scaffolds interact to form larger scaffolds and that S1A dimers group together, in the presence of CAVIN1, to form the caveolae coat.Ismail M. KhaterFanrui MengTimothy H. WongIvan Robert NabiGhassan HamarnehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ismail M. Khater Fanrui Meng Timothy H. Wong Ivan Robert Nabi Ghassan Hamarneh Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds
description	Abstract Quantitative approaches to analyze the large data sets generated by single molecule localization super-resolution microscopy (SMLM) are limited. We developed a computational pipeline and applied it to analyzing 3D point clouds of SMLM localizations (event lists) of the caveolar coat protein, caveolin-1 (Cav1), in prostate cancer cells differentially expressing CAVIN1 (also known as PTRF), that is also required for caveolae formation. High degree (strongly-interacting) points were removed by an iterative blink merging algorithm and Cav1 network properties were compared with randomly generated networks to retain a sub-network of geometric structures (or blobs). Machine-learning based classification extracted 28 quantitative features describing the size, shape, topology and network characteristics of ∼80,000 blobs. Unsupervised clustering identified small S1A scaffolds corresponding to SDS-resistant Cav1 oligomers, as yet undescribed larger hemi-spherical S2 scaffolds and, only in CAVIN1-expressing cells, spherical, hollow caveolae. Multi-threshold modularity analysis suggests that S1A scaffolds interact to form larger scaffolds and that S1A dimers group together, in the presence of CAVIN1, to form the caveolae coat.
format	article
author	Ismail M. Khater Fanrui Meng Timothy H. Wong Ivan Robert Nabi Ghassan Hamarneh
author_facet	Ismail M. Khater Fanrui Meng Timothy H. Wong Ivan Robert Nabi Ghassan Hamarneh
author_sort	Ismail M. Khater
title	Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds
title_short	Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds
title_full	Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds
title_fullStr	Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds
title_full_unstemmed	Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds
title_sort	super resolution network analysis defines the molecular architecture of caveolae and caveolin-1 scaffolds
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a27e59028cde44fbb21695413a32161e
work_keys_str_mv	AT ismailmkhater superresolutionnetworkanalysisdefinesthemoleculararchitectureofcaveolaeandcaveolin1scaffolds AT fanruimeng superresolutionnetworkanalysisdefinesthemoleculararchitectureofcaveolaeandcaveolin1scaffolds AT timothyhwong superresolutionnetworkanalysisdefinesthemoleculararchitectureofcaveolaeandcaveolin1scaffolds AT ivanrobertnabi superresolutionnetworkanalysisdefinesthemoleculararchitectureofcaveolaeandcaveolin1scaffolds AT ghassanhamarneh superresolutionnetworkanalysisdefinesthemoleculararchitectureofcaveolaeandcaveolin1scaffolds
_version_	1718388407990747136

Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds

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