Nanonet force microscopy for measuring forces in single smooth muscle cells of the human aorta

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dc.contributor.authorHall, Alexanderen
dc.contributor.authorChan, Patricken
dc.contributor.authorSheets, Kevinen
dc.contributor.authorApperson, Matthewen
dc.contributor.authorDelaughter, Christopheren
dc.contributor.authorGleason, Thomas G.en
dc.contributor.authorPhillippi, Julie A.en
dc.contributor.authorNain, Amrinder S.en
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessioned2019-10-03T17:21:57Zen
dc.date.available2019-10-03T17:21:57Zen
dc.date.issued2017-07-07en
dc.description.abstractA number of innovative methods exist to measure cell-matrix adhesive forces, but they have yet to accurately describe and quantify the intricate interplay of a cell and its fibrous extracellular matrix (ECM). In cardiovascular pathologies, such as aortic aneurysm, new knowledge on the involvement of cell-matrix forces could lead to elucidation of disease mechanisms. To better understand this dynamics, we measured primary human aortic single smooth muscle cell (SMC) forces using nanonet force microscopy in both inside-out (I-O intrinsic contractility) and outside-in (O-I external perturbation) modes. For SMC populations, we measured the I-O and O-I forces to be 12.9 +/- 1.0 and 57.9 +/- 2.5 nN, respectively. Exposure of cells to oxidative stress conditions caused a force decrease of 57 and 48% in I-O and O-I modes, respectively, and an increase in migration rate by 2.5-fold. Finally, in O-I mode, we cyclically perturbed cells at constant strain of varying duration to simulate in vivo conditions of the cardiac cycle and found that I-O forces decrease with increasing duration and O-I forces decreased by half at shorter cycle times. Thus our findings highlight the need to study forces exerted and felt by cells simultaneously to comprehensively understand force modulation in cardiovascular disease.en
dc.description.notesT.G. and J.P. gratefully acknowledge Kristin Konopka and Julie Schreiber for assistance with IRB protocols and informed patient consent, Jennifer Hill and Tara Richards for smooth muscle cell isolation, and the Center for Organ Recovery and Education for assistance in obtaining donor tissues. T.G.G. and J.P. acknowledge support by the National Heart, Lung and Blood Institute of the National Institutes of Health under Award HL 109132 (T.G.G.) and the Department of Cardiothoracic Surgery at the University of Pittsburgh. A.S.N. acknowledges support by National Science Foundation Grants CMMI-1437101 and 1462916 and the Institute for Critical Technology and Applied Sciences at Virginia Tech.en
dc.description.sponsorshipNational Heart, Lung and Blood Institute of the National Institutes of Health [HL 109132]; Department of Cardiothoracic Surgery at the University of Pittsburgh; National Science Foundation [CMMI-1437101, 1462916]; Institute for Critical Technology and Applied Sciences at Virginia Techen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1091/mbc.E17-01-0053en
dc.identifier.eissn1939-4586en
dc.identifier.issn1059-1524en
dc.identifier.issue14en
dc.identifier.pmid28450452en
dc.identifier.urihttp://hdl.handle.net/10919/94341en
dc.identifier.volume28en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.titleNanonet force microscopy for measuring forces in single smooth muscle cells of the human aortaen
dc.title.serialMolecular Biology of the Cellen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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