Plasticity in the macromolecular-scale causal networks of cell migration.

Heterogeneous and dynamic single cell migration behaviours arise from a complex multi-scale signalling network comprising both molecular components and macromolecular modules, among which cell-matrix adhesions and F-actin directly mediate migration. To date, the global wiring architecture characteri...

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Autores principales:	John G Lock, Mehrdad Jafari Mamaghani, Hamdah Shafqat-Abbasi, Xiaowei Gong, Joanna Tyrcha, Staffan Strömblad
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8242f4a16cd14b78a414665ea4073b58
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spelling	oai:doaj.org-article:8242f4a16cd14b78a414665ea4073b582021-11-18T08:30:13ZPlasticity in the macromolecular-scale causal networks of cell migration.1932-620310.1371/journal.pone.0090593https://doaj.org/article/8242f4a16cd14b78a414665ea4073b582014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587399/?tool=EBIhttps://doaj.org/toc/1932-6203Heterogeneous and dynamic single cell migration behaviours arise from a complex multi-scale signalling network comprising both molecular components and macromolecular modules, among which cell-matrix adhesions and F-actin directly mediate migration. To date, the global wiring architecture characterizing this network remains poorly defined. It is also unclear whether such a wiring pattern may be stable and generalizable to different conditions, or plastic and context dependent. Here, synchronous imaging-based quantification of migration system organization, represented by 87 morphological and dynamic macromolecular module features, and migration system behaviour, i.e., migration speed, facilitated Granger causality analysis. We thereby leveraged natural cellular heterogeneity to begin mapping the directionally specific causal wiring between organizational and behavioural features of the cell migration system. This represents an important advance on commonly used correlative analyses that do not resolve causal directionality. We identified organizational features such as adhesion stability and adhesion F-actin content that, as anticipated, causally influenced cell migration speed. Strikingly, we also found that cell speed can exert causal influence over organizational features, including cell shape and adhesion complex location, thus revealing causality in directions contradictory to previous expectations. Importantly, by comparing unperturbed and signalling-modulated cells, we provide proof-of-principle that causal interaction patterns are in fact plastic and context dependent, rather than stable and generalizable.John G LockMehrdad Jafari MamaghaniHamdah Shafqat-AbbasiXiaowei GongJoanna TyrchaStaffan StrömbladPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e90593 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John G Lock Mehrdad Jafari Mamaghani Hamdah Shafqat-Abbasi Xiaowei Gong Joanna Tyrcha Staffan Strömblad Plasticity in the macromolecular-scale causal networks of cell migration.
description	Heterogeneous and dynamic single cell migration behaviours arise from a complex multi-scale signalling network comprising both molecular components and macromolecular modules, among which cell-matrix adhesions and F-actin directly mediate migration. To date, the global wiring architecture characterizing this network remains poorly defined. It is also unclear whether such a wiring pattern may be stable and generalizable to different conditions, or plastic and context dependent. Here, synchronous imaging-based quantification of migration system organization, represented by 87 morphological and dynamic macromolecular module features, and migration system behaviour, i.e., migration speed, facilitated Granger causality analysis. We thereby leveraged natural cellular heterogeneity to begin mapping the directionally specific causal wiring between organizational and behavioural features of the cell migration system. This represents an important advance on commonly used correlative analyses that do not resolve causal directionality. We identified organizational features such as adhesion stability and adhesion F-actin content that, as anticipated, causally influenced cell migration speed. Strikingly, we also found that cell speed can exert causal influence over organizational features, including cell shape and adhesion complex location, thus revealing causality in directions contradictory to previous expectations. Importantly, by comparing unperturbed and signalling-modulated cells, we provide proof-of-principle that causal interaction patterns are in fact plastic and context dependent, rather than stable and generalizable.
format	article
author	John G Lock Mehrdad Jafari Mamaghani Hamdah Shafqat-Abbasi Xiaowei Gong Joanna Tyrcha Staffan Strömblad
author_facet	John G Lock Mehrdad Jafari Mamaghani Hamdah Shafqat-Abbasi Xiaowei Gong Joanna Tyrcha Staffan Strömblad
author_sort	John G Lock
title	Plasticity in the macromolecular-scale causal networks of cell migration.
title_short	Plasticity in the macromolecular-scale causal networks of cell migration.
title_full	Plasticity in the macromolecular-scale causal networks of cell migration.
title_fullStr	Plasticity in the macromolecular-scale causal networks of cell migration.
title_full_unstemmed	Plasticity in the macromolecular-scale causal networks of cell migration.
title_sort	plasticity in the macromolecular-scale causal networks of cell migration.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8242f4a16cd14b78a414665ea4073b58
work_keys_str_mv	AT johnglock plasticityinthemacromolecularscalecausalnetworksofcellmigration AT mehrdadjafarimamaghani plasticityinthemacromolecularscalecausalnetworksofcellmigration AT hamdahshafqatabbasi plasticityinthemacromolecularscalecausalnetworksofcellmigration AT xiaoweigong plasticityinthemacromolecularscalecausalnetworksofcellmigration AT joannatyrcha plasticityinthemacromolecularscalecausalnetworksofcellmigration AT staffanstromblad plasticityinthemacromolecularscalecausalnetworksofcellmigration
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Plasticity in the macromolecular-scale causal networks of cell migration.

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