Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD

Abstract Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII...

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Autores principales:	Karolina Mikulska-Ruminska, Andrej J. Kulik, Carine Benadiba, Ivet Bahar, Giovanni Dietler, Wieslaw Nowak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/254fe0b9248549b59a53d90c5469c122
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spelling	oai:doaj.org-article:254fe0b9248549b59a53d90c5469c1222021-12-02T12:32:52ZNanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD10.1038/s41598-017-09482-w2045-2322https://doaj.org/article/254fe0b9248549b59a53d90c5469c1222017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09482-whttps://doaj.org/toc/2045-2322Abstract Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations in CNTN4 gene have been linked to various psychiatric disorders. Toward elucidating the response of this modular protein to mechanical stress, we studied its force-induced unfolding using single molecule atomic force microscopy (smAFM) and steered molecular dynamics (SMD) simulations. Extensive smAFM and SMD data both indicate the distinctive mechanical behavior of the two types of modules distinguished by unique force-extension signatures. The data also reveal the heterogeneity of the response of the individual FNIII and IgC2 modules, which presumably plays a role in the adaptability of CNTN4 to maintaining cell-cell communication and adhesion properties under different conditions. Results show that extensive sampling of force spectra, facilitated by robot-enhanced AFM, can help reveal the existence of weak stabilizing interactions between the domains of multidomain proteins, and provide insights into the nanomechanics of such multidomain or heteromeric proteins.Karolina Mikulska-RuminskaAndrej J. KulikCarine BenadibaIvet BaharGiovanni DietlerWieslaw NowakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karolina Mikulska-Ruminska Andrej J. Kulik Carine Benadiba Ivet Bahar Giovanni Dietler Wieslaw Nowak Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
description	Abstract Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations in CNTN4 gene have been linked to various psychiatric disorders. Toward elucidating the response of this modular protein to mechanical stress, we studied its force-induced unfolding using single molecule atomic force microscopy (smAFM) and steered molecular dynamics (SMD) simulations. Extensive smAFM and SMD data both indicate the distinctive mechanical behavior of the two types of modules distinguished by unique force-extension signatures. The data also reveal the heterogeneity of the response of the individual FNIII and IgC2 modules, which presumably plays a role in the adaptability of CNTN4 to maintaining cell-cell communication and adhesion properties under different conditions. Results show that extensive sampling of force spectra, facilitated by robot-enhanced AFM, can help reveal the existence of weak stabilizing interactions between the domains of multidomain proteins, and provide insights into the nanomechanics of such multidomain or heteromeric proteins.
format	article
author	Karolina Mikulska-Ruminska Andrej J. Kulik Carine Benadiba Ivet Bahar Giovanni Dietler Wieslaw Nowak
author_facet	Karolina Mikulska-Ruminska Andrej J. Kulik Carine Benadiba Ivet Bahar Giovanni Dietler Wieslaw Nowak
author_sort	Karolina Mikulska-Ruminska
title	Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
title_short	Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
title_full	Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
title_fullStr	Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
title_full_unstemmed	Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
title_sort	nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule afm and smd
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/254fe0b9248549b59a53d90c5469c122
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Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD

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