Cardiomyocyte mechanodynamics under conditions of actin remodelling
The mechanical performance of cardiomyocytes (CMs) is an important indicator of their maturation state and of primary importance for the development of therapies based on cardiac stem cells. As the mechanical analysis of adherent cells at high-throughput remains challenging, we explore the applicabi...
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Veröffentlicht in: | Philosophical transactions of the Royal Society of London. Series B. Biological sciences 2019-11, Vol.374 (1786), p.20190081-20190081 |
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container_title | Philosophical transactions of the Royal Society of London. Series B. Biological sciences |
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creator | Pires, Ricardo H Shree, Nithya Manu, Emmanuel Guzniczak, Ewa Otto, Oliver |
description | The mechanical performance of cardiomyocytes (CMs) is an important indicator of their maturation state and of primary importance for the development of therapies based on cardiac stem cells. As the mechanical analysis of adherent cells at high-throughput remains challenging, we explore the applicability of real-time deformability cytometry (RT-DC) to probe cardiomyocytes in suspension. RT-DC is a microfluidic technology allowing for real-time mechanical analysis of thousands of cells with a throughput exceeding 1000 cells per second. For CMs derived from human-induced pluripotent stem cells, we determined a Young's modulus of 1.25 ± 0.08 kPa which is in close range to previous reports. Upon challenging the cytoskeleton with cytochalasin D (CytoD) to induce filamentous actin depolymerization, we distinguish three different regimes in cellular elasticity. Transitions are observed below 10 nM and above 10
nM and are characterized by a decrease in Young's modulus. These regimes can be linked to cytoskeletal and sarcomeric actin contributions by CM contractility measurements at varying CytoD concentrations, where we observe a significant reduction in pulse duration only above 10
nM while no change is found for compound exposure at lower concentrations. Comparing our results to mechanical cell measurements using atomic force microscopy, we demonstrate for the first time to our knowledge, the feasibility of using a microfluidic technique to measure mechanical properties of large samples of adherent cells while linking our results to the composition of the cytoskeletal network. This article is part of a discussion meeting issue 'Single cell ecology'. |
doi_str_mv | 10.1098/rstb.2019.0081 |
format | Article |
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nM and are characterized by a decrease in Young's modulus. These regimes can be linked to cytoskeletal and sarcomeric actin contributions by CM contractility measurements at varying CytoD concentrations, where we observe a significant reduction in pulse duration only above 10
nM while no change is found for compound exposure at lower concentrations. Comparing our results to mechanical cell measurements using atomic force microscopy, we demonstrate for the first time to our knowledge, the feasibility of using a microfluidic technique to measure mechanical properties of large samples of adherent cells while linking our results to the composition of the cytoskeletal network. This article is part of a discussion meeting issue 'Single cell ecology'.</description><identifier>ISSN: 0962-8436</identifier><identifier>EISSN: 1471-2970</identifier><identifier>DOI: 10.1098/rstb.2019.0081</identifier><identifier>PMID: 31587648</identifier><language>eng</language><publisher>England: The Royal Society</publisher><ispartof>Philosophical transactions of the Royal Society of London. Series B. Biological sciences, 2019-11, Vol.374 (1786), p.20190081-20190081</ispartof><rights>2019 The Authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-8131ee5b5041adf2e11e29ea38c8ee8537cf232f2bd8e2df7d401ea308dfa76b3</citedby><cites>FETCH-LOGICAL-c539t-8131ee5b5041adf2e11e29ea38c8ee8537cf232f2bd8e2df7d401ea308dfa76b3</cites><orcidid>0000-0003-0280-5374</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792454/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792454/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,887,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31587648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pires, Ricardo H</creatorcontrib><creatorcontrib>Shree, Nithya</creatorcontrib><creatorcontrib>Manu, Emmanuel</creatorcontrib><creatorcontrib>Guzniczak, Ewa</creatorcontrib><creatorcontrib>Otto, Oliver</creatorcontrib><title>Cardiomyocyte mechanodynamics under conditions of actin remodelling</title><title>Philosophical transactions of the Royal Society of London. Series B. Biological sciences</title><addtitle>Philos Trans R Soc Lond B Biol Sci</addtitle><description>The mechanical performance of cardiomyocytes (CMs) is an important indicator of their maturation state and of primary importance for the development of therapies based on cardiac stem cells. As the mechanical analysis of adherent cells at high-throughput remains challenging, we explore the applicability of real-time deformability cytometry (RT-DC) to probe cardiomyocytes in suspension. RT-DC is a microfluidic technology allowing for real-time mechanical analysis of thousands of cells with a throughput exceeding 1000 cells per second. For CMs derived from human-induced pluripotent stem cells, we determined a Young's modulus of 1.25 ± 0.08 kPa which is in close range to previous reports. Upon challenging the cytoskeleton with cytochalasin D (CytoD) to induce filamentous actin depolymerization, we distinguish three different regimes in cellular elasticity. Transitions are observed below 10 nM and above 10
nM and are characterized by a decrease in Young's modulus. These regimes can be linked to cytoskeletal and sarcomeric actin contributions by CM contractility measurements at varying CytoD concentrations, where we observe a significant reduction in pulse duration only above 10
nM while no change is found for compound exposure at lower concentrations. Comparing our results to mechanical cell measurements using atomic force microscopy, we demonstrate for the first time to our knowledge, the feasibility of using a microfluidic technique to measure mechanical properties of large samples of adherent cells while linking our results to the composition of the cytoskeletal network. This article is part of a discussion meeting issue 'Single cell ecology'.</description><issn>0962-8436</issn><issn>1471-2970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVkEtPwzAQhC0EoqVw5Yhy5JLgRx72BQlVvKRKXOBsOfamNUrsYidI_fckaqngtIeZnd35ELomOCNY8LsQ-zqjmIgMY05O0JzkFUmpqPApmmNR0pTnrJyhixg_McaiqPJzNGOk4FWZ8zlaLlUw1nc7r3c9JB3ojXLe7JzqrI7J4AyERHtnbG-9i4lvEqV765IAnTfQttatL9FZo9oIV4e5QB9Pj-_Ll3T19vy6fFilumCiTzlhBKCoC5wTZRoKhAAVoBjXHIAXrNINZbShteFATVOZHJNRxtw0qiprtkD3-9ztUHdgNLg-qFZug-1U2EmvrPyvOLuRa_8ty0rQvMjHgNtDQPBfA8RedjbqsYRy4IcoKcOEc0E5G63Z3qqDjzFAczxDsJzIy4m8nMjLify4cPP3uaP9FzX7Afoqgn0</recordid><startdate>20191125</startdate><enddate>20191125</enddate><creator>Pires, Ricardo H</creator><creator>Shree, Nithya</creator><creator>Manu, Emmanuel</creator><creator>Guzniczak, Ewa</creator><creator>Otto, Oliver</creator><general>The Royal Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0280-5374</orcidid></search><sort><creationdate>20191125</creationdate><title>Cardiomyocyte mechanodynamics under conditions of actin remodelling</title><author>Pires, Ricardo H ; Shree, Nithya ; Manu, Emmanuel ; Guzniczak, Ewa ; Otto, Oliver</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-8131ee5b5041adf2e11e29ea38c8ee8537cf232f2bd8e2df7d401ea308dfa76b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pires, Ricardo H</creatorcontrib><creatorcontrib>Shree, Nithya</creatorcontrib><creatorcontrib>Manu, Emmanuel</creatorcontrib><creatorcontrib>Guzniczak, Ewa</creatorcontrib><creatorcontrib>Otto, Oliver</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Philosophical transactions of the Royal Society of London. Series B. Biological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pires, Ricardo H</au><au>Shree, Nithya</au><au>Manu, Emmanuel</au><au>Guzniczak, Ewa</au><au>Otto, Oliver</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardiomyocyte mechanodynamics under conditions of actin remodelling</atitle><jtitle>Philosophical transactions of the Royal Society of London. Series B. Biological sciences</jtitle><addtitle>Philos Trans R Soc Lond B Biol Sci</addtitle><date>2019-11-25</date><risdate>2019</risdate><volume>374</volume><issue>1786</issue><spage>20190081</spage><epage>20190081</epage><pages>20190081-20190081</pages><issn>0962-8436</issn><eissn>1471-2970</eissn><abstract>The mechanical performance of cardiomyocytes (CMs) is an important indicator of their maturation state and of primary importance for the development of therapies based on cardiac stem cells. As the mechanical analysis of adherent cells at high-throughput remains challenging, we explore the applicability of real-time deformability cytometry (RT-DC) to probe cardiomyocytes in suspension. RT-DC is a microfluidic technology allowing for real-time mechanical analysis of thousands of cells with a throughput exceeding 1000 cells per second. For CMs derived from human-induced pluripotent stem cells, we determined a Young's modulus of 1.25 ± 0.08 kPa which is in close range to previous reports. Upon challenging the cytoskeleton with cytochalasin D (CytoD) to induce filamentous actin depolymerization, we distinguish three different regimes in cellular elasticity. Transitions are observed below 10 nM and above 10
nM and are characterized by a decrease in Young's modulus. These regimes can be linked to cytoskeletal and sarcomeric actin contributions by CM contractility measurements at varying CytoD concentrations, where we observe a significant reduction in pulse duration only above 10
nM while no change is found for compound exposure at lower concentrations. Comparing our results to mechanical cell measurements using atomic force microscopy, we demonstrate for the first time to our knowledge, the feasibility of using a microfluidic technique to measure mechanical properties of large samples of adherent cells while linking our results to the composition of the cytoskeletal network. This article is part of a discussion meeting issue 'Single cell ecology'.</abstract><cop>England</cop><pub>The Royal Society</pub><pmid>31587648</pmid><doi>10.1098/rstb.2019.0081</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0280-5374</orcidid><oa>free_for_read</oa></addata></record> |
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title | Cardiomyocyte mechanodynamics under conditions of actin remodelling |
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