Cell spheroid fusion: beyond liquid drops model
Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell...
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creator | Kosheleva, Nastasia V. Efremov, Yuri M. Shavkuta, Boris S. Zurina, Irina M. Zhang, Deying Zhang, Yuanyuan Minaev, Nikita V. Gorkun, Anastasiya A. Wei, Shicheng Shpichka, Anastasia I. Saburina, Irina N. Timashev, Peter S. |
description | Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. This discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation. |
doi_str_mv | 10.1038/s41598-020-69540-8 |
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The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. This discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-69540-8</identifier><identifier>PMID: 32724115</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/532/2118/2074 ; 631/61/490 ; 692/308/2171 ; Aggregates ; Biomarkers - metabolism ; Cell adhesion & migration ; Cell Fusion ; Cell migration ; Cell Shape ; Cells, Cultured ; Coalescence ; Elastic Modulus ; Epithelial Cells - cytology ; Epithelial Cells - ultrastructure ; Epithelium ; Extracellular matrix ; Humanities and Social Sciences ; Humans ; Limbus Corneae - cytology ; Mechanical properties ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - ultrastructure ; Mesenchyme ; Models, Biological ; multidisciplinary ; Phenotypes ; Retinal pigment epithelium ; Retinal Pigment Epithelium - cytology ; Science ; Science (multidisciplinary) ; Self-assembly ; Somatic cells ; Spheroids ; Spheroids, Cellular - cytology ; Stem cells ; Stroma ; Surface tension ; Tissue engineering</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.12614-12614, Article 12614</ispartof><rights>The Author(s) 2020. corrected publication 2021</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020. corrected publication 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020, corrected publication 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-329704725407aaf452eeba114bee9fc5e3035e48cd0c99fe28fa68426f7602153</citedby><cites>FETCH-LOGICAL-c539t-329704725407aaf452eeba114bee9fc5e3035e48cd0c99fe28fa68426f7602153</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387529/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387529/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32724115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kosheleva, Nastasia V.</creatorcontrib><creatorcontrib>Efremov, Yuri M.</creatorcontrib><creatorcontrib>Shavkuta, Boris S.</creatorcontrib><creatorcontrib>Zurina, Irina M.</creatorcontrib><creatorcontrib>Zhang, Deying</creatorcontrib><creatorcontrib>Zhang, Yuanyuan</creatorcontrib><creatorcontrib>Minaev, Nikita V.</creatorcontrib><creatorcontrib>Gorkun, Anastasiya A.</creatorcontrib><creatorcontrib>Wei, Shicheng</creatorcontrib><creatorcontrib>Shpichka, Anastasia I.</creatorcontrib><creatorcontrib>Saburina, Irina N.</creatorcontrib><creatorcontrib>Timashev, Peter S.</creatorcontrib><title>Cell spheroid fusion: beyond liquid drops model</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. This discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation.</description><subject>631/532/2118/2074</subject><subject>631/61/490</subject><subject>692/308/2171</subject><subject>Aggregates</subject><subject>Biomarkers - metabolism</subject><subject>Cell adhesion & migration</subject><subject>Cell Fusion</subject><subject>Cell migration</subject><subject>Cell Shape</subject><subject>Cells, Cultured</subject><subject>Coalescence</subject><subject>Elastic Modulus</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - ultrastructure</subject><subject>Epithelium</subject><subject>Extracellular matrix</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Limbus Corneae - cytology</subject><subject>Mechanical properties</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - ultrastructure</subject><subject>Mesenchyme</subject><subject>Models, Biological</subject><subject>multidisciplinary</subject><subject>Phenotypes</subject><subject>Retinal pigment epithelium</subject><subject>Retinal Pigment Epithelium - cytology</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Self-assembly</subject><subject>Somatic cells</subject><subject>Spheroids</subject><subject>Spheroids, Cellular - cytology</subject><subject>Stem cells</subject><subject>Stroma</subject><subject>Surface tension</subject><subject>Tissue engineering</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1LAzEQhoMotqh_wIMsePGyNpkkm8SDIMUvKHjRc0h3Z-2W7aZNuoL_3mj9PjSXhMwz78zLS8gxo-eMcj2Kgkmjcwo0L4wUNNc7ZAhUyBw4wO6v94AcxTin6Ugwgpl9MuCgQDAmh2Q0xrbN4nKGwTdVVvex8d1FNsVX31VZ26z69FsFv4zZwlfYHpK92rURjz7vA_J0c_04vssnD7f346tJXkpu1jkHo6hQkBZTztVCAuLUMSamiKYuJXLKJQpdVrQ0pkbQtSu0gKJWBQUm-QG53Ogu--kCqxK7dXCtXYZm4cKr9a6xfytdM7PP_sUqrlXymQTOPgWCX_UY13bRxDKZdR36PloQoAVTivGEnv5D574PXbJnQUrFqaRGbaUEKMmFYUWiYEOVwccYsP5emVH7HpzdBGdTcPYjOKtT08lvs98tXzElgG-AmErdM4af2Vtk3wCWbqEg</recordid><startdate>20200728</startdate><enddate>20200728</enddate><creator>Kosheleva, Nastasia V.</creator><creator>Efremov, Yuri M.</creator><creator>Shavkuta, Boris S.</creator><creator>Zurina, Irina M.</creator><creator>Zhang, Deying</creator><creator>Zhang, Yuanyuan</creator><creator>Minaev, Nikita V.</creator><creator>Gorkun, Anastasiya A.</creator><creator>Wei, Shicheng</creator><creator>Shpichka, Anastasia I.</creator><creator>Saburina, Irina N.</creator><creator>Timashev, Peter S.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200728</creationdate><title>Cell spheroid fusion: beyond liquid drops model</title><author>Kosheleva, Nastasia V. ; Efremov, Yuri M. ; Shavkuta, Boris S. ; Zurina, Irina M. ; Zhang, Deying ; Zhang, Yuanyuan ; Minaev, Nikita V. ; Gorkun, Anastasiya A. ; Wei, Shicheng ; Shpichka, Anastasia I. ; Saburina, Irina N. ; Timashev, Peter S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-329704725407aaf452eeba114bee9fc5e3035e48cd0c99fe28fa68426f7602153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/532/2118/2074</topic><topic>631/61/490</topic><topic>692/308/2171</topic><topic>Aggregates</topic><topic>Biomarkers - metabolism</topic><topic>Cell adhesion & migration</topic><topic>Cell Fusion</topic><topic>Cell migration</topic><topic>Cell Shape</topic><topic>Cells, Cultured</topic><topic>Coalescence</topic><topic>Elastic Modulus</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - ultrastructure</topic><topic>Epithelium</topic><topic>Extracellular matrix</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Limbus Corneae - cytology</topic><topic>Mechanical properties</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - ultrastructure</topic><topic>Mesenchyme</topic><topic>Models, Biological</topic><topic>multidisciplinary</topic><topic>Phenotypes</topic><topic>Retinal pigment epithelium</topic><topic>Retinal Pigment Epithelium - cytology</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Self-assembly</topic><topic>Somatic cells</topic><topic>Spheroids</topic><topic>Spheroids, Cellular - cytology</topic><topic>Stem cells</topic><topic>Stroma</topic><topic>Surface tension</topic><topic>Tissue engineering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kosheleva, Nastasia V.</creatorcontrib><creatorcontrib>Efremov, Yuri M.</creatorcontrib><creatorcontrib>Shavkuta, Boris S.</creatorcontrib><creatorcontrib>Zurina, Irina M.</creatorcontrib><creatorcontrib>Zhang, Deying</creatorcontrib><creatorcontrib>Zhang, Yuanyuan</creatorcontrib><creatorcontrib>Minaev, Nikita V.</creatorcontrib><creatorcontrib>Gorkun, Anastasiya A.</creatorcontrib><creatorcontrib>Wei, Shicheng</creatorcontrib><creatorcontrib>Shpichka, Anastasia I.</creatorcontrib><creatorcontrib>Saburina, Irina N.</creatorcontrib><creatorcontrib>Timashev, Peter S.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kosheleva, Nastasia V.</au><au>Efremov, Yuri M.</au><au>Shavkuta, Boris S.</au><au>Zurina, Irina M.</au><au>Zhang, Deying</au><au>Zhang, Yuanyuan</au><au>Minaev, Nikita V.</au><au>Gorkun, Anastasiya A.</au><au>Wei, Shicheng</au><au>Shpichka, Anastasia I.</au><au>Saburina, Irina N.</au><au>Timashev, Peter S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cell spheroid fusion: beyond liquid drops model</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-28</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>12614</spage><epage>12614</epage><pages>12614-12614</pages><artnum>12614</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. This discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32724115</pmid><doi>10.1038/s41598-020-69540-8</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 631/532/2118/2074 631/61/490 692/308/2171 Aggregates Biomarkers - metabolism Cell adhesion & migration Cell Fusion Cell migration Cell Shape Cells, Cultured Coalescence Elastic Modulus Epithelial Cells - cytology Epithelial Cells - ultrastructure Epithelium Extracellular matrix Humanities and Social Sciences Humans Limbus Corneae - cytology Mechanical properties Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - ultrastructure Mesenchyme Models, Biological multidisciplinary Phenotypes Retinal pigment epithelium Retinal Pigment Epithelium - cytology Science Science (multidisciplinary) Self-assembly Somatic cells Spheroids Spheroids, Cellular - cytology Stem cells Stroma Surface tension Tissue engineering |
title | Cell spheroid fusion: beyond liquid drops model |
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