Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride

AM Kolodziejczyk,1 GD Brzezinka,1 K Khurana,1,2 M Targosz-Korecka,1 M Szymonski11Research Centre for Nanometer-Scale Science and Advanced Materials, NANOSAM, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Krakow, Poland; 2Centre for Environmental Risk Assessment...

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Autores principales:	Kolodziejczyk AM, Brzezinka GD, Khurana K, Targosz-Korecka M, Szymonski M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/177229360ed84d4c80934bd458657d53
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spelling	oai:doaj.org-article:177229360ed84d4c80934bd458657d532021-12-02T07:36:59ZNanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride1176-91141178-2013https://doaj.org/article/177229360ed84d4c80934bd458657d532013-08-01T00:00:00Zhttp://www.dovepress.com/nanomechanical-sensing-of-the-endothelial-cell-response-to-anti-inflam-a13872https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013AM Kolodziejczyk,1 GD Brzezinka,1 K Khurana,1,2 M Targosz-Korecka,1 M Szymonski11Research Centre for Nanometer-Scale Science and Advanced Materials, NANOSAM, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Krakow, Poland; 2Centre for Environmental Risk Assessment and Remediation (CERAR), University of South Australia, AustraliaBackground: There is increasing evidence that cell elastic properties should change considerably in response to chemical agents affecting the physiological state of the endothelium. In this work, a novel assay for testing prospective endothelium-targeted agents in vitro is presented.Materials and methods: The proposed methodology is based on nanoindentation spectroscopy using an atomic force microscope tip, which allows for quantitative evaluation of cell stiffness. As an example, we chose a pyridine derivative, 1-methylnicotinamide chloride (MNA), known to have antithrombotic and anti-inflammatory properties, as reported in recent in vivo experiments.Results: First, we determined a concentration range of MNA in which physiological parameters of the endothelial cells in vitro are not affected. Then, cell dysfunction was induced by incubation with tumor necrosis factor-alpha (TNF-α) and the cellular response to MNA treatment after TNF-α incubation was studied. In parallel to the nanoindentation spectroscopy, the endothelium phenotype was characterized using a fluorescence spectroscopy with F-actin labeling, and biochemical methods, such as secretion measurements of both nitric oxide (NO), and prostacyclin (PGI2) regulatory agents.Conclusion: We found that MNA could reverse the dysfunction of the endothelium caused by inflammation, if applied in the proper time and to the concentration scheme established in our investigations. A surprisingly close correlation was found between effective Young's modulus of the cells and actin polymerization/depolymerization processes in the endothelium cortical cytoskeleton, as well as NO and PGI2 levels. These results allow us to construct the physiological model of sequential intracellular pathways activated in the endothelium by MNA.Keywords: endothelium, cell stiffness, 1-methylnicotinamide chloride, atomic force microscopy, nanomechanical sensingKolodziejczyk AMBrzezinka GDKhurana KTargosz-Korecka MSzymonski MDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2757-2767 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kolodziejczyk AM Brzezinka GD Khurana K Targosz-Korecka M Szymonski M Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
description	AM Kolodziejczyk,1 GD Brzezinka,1 K Khurana,1,2 M Targosz-Korecka,1 M Szymonski11Research Centre for Nanometer-Scale Science and Advanced Materials, NANOSAM, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Krakow, Poland; 2Centre for Environmental Risk Assessment and Remediation (CERAR), University of South Australia, AustraliaBackground: There is increasing evidence that cell elastic properties should change considerably in response to chemical agents affecting the physiological state of the endothelium. In this work, a novel assay for testing prospective endothelium-targeted agents in vitro is presented.Materials and methods: The proposed methodology is based on nanoindentation spectroscopy using an atomic force microscope tip, which allows for quantitative evaluation of cell stiffness. As an example, we chose a pyridine derivative, 1-methylnicotinamide chloride (MNA), known to have antithrombotic and anti-inflammatory properties, as reported in recent in vivo experiments.Results: First, we determined a concentration range of MNA in which physiological parameters of the endothelial cells in vitro are not affected. Then, cell dysfunction was induced by incubation with tumor necrosis factor-alpha (TNF-α) and the cellular response to MNA treatment after TNF-α incubation was studied. In parallel to the nanoindentation spectroscopy, the endothelium phenotype was characterized using a fluorescence spectroscopy with F-actin labeling, and biochemical methods, such as secretion measurements of both nitric oxide (NO), and prostacyclin (PGI2) regulatory agents.Conclusion: We found that MNA could reverse the dysfunction of the endothelium caused by inflammation, if applied in the proper time and to the concentration scheme established in our investigations. A surprisingly close correlation was found between effective Young's modulus of the cells and actin polymerization/depolymerization processes in the endothelium cortical cytoskeleton, as well as NO and PGI2 levels. These results allow us to construct the physiological model of sequential intracellular pathways activated in the endothelium by MNA.Keywords: endothelium, cell stiffness, 1-methylnicotinamide chloride, atomic force microscopy, nanomechanical sensing
format	article
author	Kolodziejczyk AM Brzezinka GD Khurana K Targosz-Korecka M Szymonski M
author_facet	Kolodziejczyk AM Brzezinka GD Khurana K Targosz-Korecka M Szymonski M
author_sort	Kolodziejczyk AM
title	Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
title_short	Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
title_full	Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
title_fullStr	Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
title_full_unstemmed	Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
title_sort	nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/177229360ed84d4c80934bd458657d53
work_keys_str_mv	AT kolodziejczykam nanomechanicalsensingoftheendothelialcellresponsetoantiinflammatoryactionof1methylnicotinamidechloride AT brzezinkagd nanomechanicalsensingoftheendothelialcellresponsetoantiinflammatoryactionof1methylnicotinamidechloride AT khuranak nanomechanicalsensingoftheendothelialcellresponsetoantiinflammatoryactionof1methylnicotinamidechloride AT targoszkoreckam nanomechanicalsensingoftheendothelialcellresponsetoantiinflammatoryactionof1methylnicotinamidechloride AT szymonskim nanomechanicalsensingoftheendothelialcellresponsetoantiinflammatoryactionof1methylnicotinamidechloride
_version_	1718399322996867072

Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride

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