Nanomechanical sensing of the endothelial cell response to anti-inflammatory action of 1-methylnicotinamide chloride
Authors Kolodziejczyk AM, Brzezinka GD, Khurana K, Targosz-Korecka M, Szymonski M
Received 19 April 2013
Accepted for publication 31 May 2013
Published 1 August 2013 Volume 2013:8(1) Pages 2757—2767
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
AM Kolodziejczyk,1 GD Brzezinka,1 K Khurana,1,2 M Targosz-Korecka,1 M Szymonski1
1Research 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, Australia
Background: 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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]
Readers of this article also read:
Can combined use of low-level lasers and hyaluronic acid injections prolong the longevity of degenerative knee joints?
Ip D, Fu NY
Published Date: 5 August 2015
Relapsed Hodgkin lymphoma in adolescents: focus on current high-dose chemotherapy and autologous stem cell transplant
Guilcher GM, Stewart DA
Published Date: 8 May 2014
Ashwanikumar N, Kumar NA, Nair SA, Kumar GS
Published Date: 15 November 2012
A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone
Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W
Published Date: 12 November 2012
Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS
Published Date: 27 July 2012
Zhai G, Aref Eshghi E
Published Date: 29 June 2012
Published Date: 8 December 2011
Niklas Schuelert, Fiona A Russell, Jason J McDougall
Published Date: 6 February 2011
Published Date: 17 September 2010
Characterization of complexation of poly (N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate) thermoresponsive cationic nanogels with salmon sperm DNA
Jim Moselhy, Tasnim Vira, Fei-Fei Liu, et al
Published Date: 24 August 2009