Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids-Older spheroids reduce interstitial space and become stiffer

Multicellular cancer spheroids are an in vitro tissue model that mimics the three-dimensional microenvironment. As spheroids grow, they develop the gradients of oxygen, nutrients, and catabolites, affecting crucial tumor characteristics such as proliferation and treatment responses. The measurement...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2023-05, Vol.18 (5), p.e0286291-e0286291
Main Authors: Madhavan, Mathangi, Jaiswal, Devina, Karlberg, Sarah, Duggan, Alexis, Almarshad, Hassan A, Claffey, Kevin P, Hoshino, Kazunori
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Breast cancer
Cancer therapies
Care and treatment
Catabolites
Cell culture
Cells
Diameters
Drug delivery systems
Drugs
Electron microscopy
Evaluation
Growth models
Humans
Hypoxia
Image resolution
Mechanical properties
Medical equipment and supplies industry
Medical imaging
Medical test kit industry
Medicine and Health Sciences
Metabolism
Methylene blue
Microenvironments
Microscopy
Microscopy, Electron
Modulus of elasticity
Multicellular tumor spheroids
Neoplasms
Nutrients
Oxygen
Patient outcomes
Physical Sciences
Physiology
Radiation
Research and Analysis Methods
Spheroids
Spheroids, Cellular
Stiffness
Transmission electron microscopy
Tumor Microenvironment
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c693t-3e81e1370ac4b2a259cbb613642d7d27249a1dd6aa63359b8b715685f716db9f3
cites cdi_FETCH-LOGICAL-c693t-3e81e1370ac4b2a259cbb613642d7d27249a1dd6aa63359b8b715685f716db9f3
container_end_page e0286291
container_issue 5
container_start_page e0286291
container_title PloS one
container_volume 18
creator Madhavan, Mathangi
Jaiswal, Devina
Karlberg, Sarah
Duggan, Alexis
Almarshad, Hassan A
Claffey, Kevin P
Hoshino, Kazunori
description Multicellular cancer spheroids are an in vitro tissue model that mimics the three-dimensional microenvironment. As spheroids grow, they develop the gradients of oxygen, nutrients, and catabolites, affecting crucial tumor characteristics such as proliferation and treatment responses. The measurement of spheroid stiffness provides a quantitative measure to evaluate such structural changes over time. In this report, we measured the stiffness of size-matched day 5 and day 20 tumor spheroids using a custom-built microscale force sensor and conducted transmission electron microscopy (TEM) imaging to compare the internal structures. We found that older spheroids reduce interstitial spaces in the core region and became significantly stiffer. The measured elastic moduli were 260±100 and 680±150 Pa, for day 5 and day 20 spheroids, respectively. The day 20 spheroids showed an optically dark region in the center. Analyzing the high-resolution TEM images of spheroid middle sections across the diameter showed that the cells in the inner region of the day 20 spheroids are significantly larger and more closely packed than those in the outer regions. On the other hand, the day 5 spheroids did not show a significant difference between the inner and outer regions. The observed reduction of the interstitial space may be one factor that contributes to stiffer older spheroids.
doi_str_mv 10.1371/journal.pone.0286291
format article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2819261079</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A750653743</galeid><doaj_id>oai_doaj_org_article_687c4f3c5e6b463ea48b74b340c34d12</doaj_id><sourcerecordid>A750653743</sourcerecordid><originalsourceid>FETCH-LOGICAL-c693t-3e81e1370ac4b2a259cbb613642d7d27249a1dd6aa63359b8b715685f716db9f3</originalsourceid><addsrcrecordid>eNqNk89u1DAQxiMEoqXwBggiISE47OI_iZOcUFUKrFRpJShcLceeZF05cWo7iPIwPCsOm1Yb1APKIc74N9_En2eS5DlGa0wL_O7Kjq4XZj3YHtaIlIxU-EFyjCtKVowg-vBgfZQ88f4KoZyWjD1OjmhBSIlpdZz8Pjcgg7N92mnprJd2uEl1J1rdt6noVdqB3IleS2HSuHBCBnD6lwg6ptgmvcyKD2k3mqAlGDMa4dIwdtalftiBs1r51dYoOPhOHahRQqr7qOSDDjpK-0HE0FSvBmk7SONG04B7mjxqhPHwbH6fJN8-nl-efV5dbD9tzk4vVpJVNKwolBiiK0jIrCaC5JWsa4Ypy4gqFClIVgmsFBOCUZpXdVkXOGdl3hSYqbpq6Enycq87GOv5bK3n0aSKMIyKKhKbPaGsuOKDix65G26F5n8D1rVcuOiCAc7KQmYNlTmwOmMURBbrZTXNkKSZwiRqvZ-rjXUHSkIfnDAL0eVOr3e8tT84RgQTVBZR4c2s4Oz1CD7wTvvpBkQPdpx-nKDYE3k-FXv1D3r_8WaqFfEEum9sLCwnUX5a5IjltMhopNb3UPFRENsnNmKjY3yR8HaREJkAP0MrRu_55uuX_2e335fs6wN2B8KEnbdmnNrSL8FsD07N7R00dy5jxKc5unWDT3PE5zmKaS8Ob-gu6XZw6B-ZKxrU</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2819261079</pqid></control><display><type>article</type><title>Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids-Older spheroids reduce interstitial space and become stiffer</title><source>PubMed Central</source><source>ProQuest Publicly Available Content database</source><creator>Madhavan, Mathangi ; Jaiswal, Devina ; Karlberg, Sarah ; Duggan, Alexis ; Almarshad, Hassan A ; Claffey, Kevin P ; Hoshino, Kazunori</creator><contributor>Weihs, Daphne</contributor><creatorcontrib>Madhavan, Mathangi ; Jaiswal, Devina ; Karlberg, Sarah ; Duggan, Alexis ; Almarshad, Hassan A ; Claffey, Kevin P ; Hoshino, Kazunori ; Weihs, Daphne</creatorcontrib><description>Multicellular cancer spheroids are an in vitro tissue model that mimics the three-dimensional microenvironment. As spheroids grow, they develop the gradients of oxygen, nutrients, and catabolites, affecting crucial tumor characteristics such as proliferation and treatment responses. The measurement of spheroid stiffness provides a quantitative measure to evaluate such structural changes over time. In this report, we measured the stiffness of size-matched day 5 and day 20 tumor spheroids using a custom-built microscale force sensor and conducted transmission electron microscopy (TEM) imaging to compare the internal structures. We found that older spheroids reduce interstitial spaces in the core region and became significantly stiffer. The measured elastic moduli were 260±100 and 680±150 Pa, for day 5 and day 20 spheroids, respectively. The day 20 spheroids showed an optically dark region in the center. Analyzing the high-resolution TEM images of spheroid middle sections across the diameter showed that the cells in the inner region of the day 20 spheroids are significantly larger and more closely packed than those in the outer regions. On the other hand, the day 5 spheroids did not show a significant difference between the inner and outer regions. The observed reduction of the interstitial space may be one factor that contributes to stiffer older spheroids.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0286291</identifier><identifier>PMID: 37228139</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and Life Sciences ; Breast cancer ; Cancer therapies ; Care and treatment ; Catabolites ; Cell culture ; Cells ; Diameters ; Drug delivery systems ; Drugs ; Electron microscopy ; Evaluation ; Growth models ; Humans ; Hypoxia ; Image resolution ; Mechanical properties ; Medical equipment and supplies industry ; Medical imaging ; Medical test kit industry ; Medicine and Health Sciences ; Metabolism ; Methylene blue ; Microenvironments ; Microscopy ; Microscopy, Electron ; Modulus of elasticity ; Multicellular tumor spheroids ; Neoplasms ; Nutrients ; Oxygen ; Patient outcomes ; Physical Sciences ; Physiology ; Radiation ; Research and Analysis Methods ; Spheroids ; Spheroids, Cellular ; Stiffness ; Transmission electron microscopy ; Tumor Microenvironment ; Tumors</subject><ispartof>PloS one, 2023-05, Vol.18 (5), p.e0286291-e0286291</ispartof><rights>Copyright: © 2023 Madhavan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Madhavan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Madhavan et al 2023 Madhavan et al</rights><rights>2023 Madhavan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c693t-3e81e1370ac4b2a259cbb613642d7d27249a1dd6aa63359b8b715685f716db9f3</citedby><cites>FETCH-LOGICAL-c693t-3e81e1370ac4b2a259cbb613642d7d27249a1dd6aa63359b8b715685f716db9f3</cites><orcidid>0000-0002-7080-7825</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2819261079/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2819261079?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37228139$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Weihs, Daphne</contributor><creatorcontrib>Madhavan, Mathangi</creatorcontrib><creatorcontrib>Jaiswal, Devina</creatorcontrib><creatorcontrib>Karlberg, Sarah</creatorcontrib><creatorcontrib>Duggan, Alexis</creatorcontrib><creatorcontrib>Almarshad, Hassan A</creatorcontrib><creatorcontrib>Claffey, Kevin P</creatorcontrib><creatorcontrib>Hoshino, Kazunori</creatorcontrib><title>Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids-Older spheroids reduce interstitial space and become stiffer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Multicellular cancer spheroids are an in vitro tissue model that mimics the three-dimensional microenvironment. As spheroids grow, they develop the gradients of oxygen, nutrients, and catabolites, affecting crucial tumor characteristics such as proliferation and treatment responses. The measurement of spheroid stiffness provides a quantitative measure to evaluate such structural changes over time. In this report, we measured the stiffness of size-matched day 5 and day 20 tumor spheroids using a custom-built microscale force sensor and conducted transmission electron microscopy (TEM) imaging to compare the internal structures. We found that older spheroids reduce interstitial spaces in the core region and became significantly stiffer. The measured elastic moduli were 260±100 and 680±150 Pa, for day 5 and day 20 spheroids, respectively. The day 20 spheroids showed an optically dark region in the center. Analyzing the high-resolution TEM images of spheroid middle sections across the diameter showed that the cells in the inner region of the day 20 spheroids are significantly larger and more closely packed than those in the outer regions. On the other hand, the day 5 spheroids did not show a significant difference between the inner and outer regions. The observed reduction of the interstitial space may be one factor that contributes to stiffer older spheroids.</description><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Catabolites</subject><subject>Cell culture</subject><subject>Cells</subject><subject>Diameters</subject><subject>Drug delivery systems</subject><subject>Drugs</subject><subject>Electron microscopy</subject><subject>Evaluation</subject><subject>Growth models</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Image resolution</subject><subject>Mechanical properties</subject><subject>Medical equipment and supplies industry</subject><subject>Medical imaging</subject><subject>Medical test kit industry</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Methylene blue</subject><subject>Microenvironments</subject><subject>Microscopy</subject><subject>Microscopy, Electron</subject><subject>Modulus of elasticity</subject><subject>Multicellular tumor spheroids</subject><subject>Neoplasms</subject><subject>Nutrients</subject><subject>Oxygen</subject><subject>Patient outcomes</subject><subject>Physical Sciences</subject><subject>Physiology</subject><subject>Radiation</subject><subject>Research and Analysis Methods</subject><subject>Spheroids</subject><subject>Spheroids, Cellular</subject><subject>Stiffness</subject><subject>Transmission electron microscopy</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk89u1DAQxiMEoqXwBggiISE47OI_iZOcUFUKrFRpJShcLceeZF05cWo7iPIwPCsOm1Yb1APKIc74N9_En2eS5DlGa0wL_O7Kjq4XZj3YHtaIlIxU-EFyjCtKVowg-vBgfZQ88f4KoZyWjD1OjmhBSIlpdZz8Pjcgg7N92mnprJd2uEl1J1rdt6noVdqB3IleS2HSuHBCBnD6lwg6ptgmvcyKD2k3mqAlGDMa4dIwdtalftiBs1r51dYoOPhOHahRQqr7qOSDDjpK-0HE0FSvBmk7SONG04B7mjxqhPHwbH6fJN8-nl-efV5dbD9tzk4vVpJVNKwolBiiK0jIrCaC5JWsa4Ypy4gqFClIVgmsFBOCUZpXdVkXOGdl3hSYqbpq6Enycq87GOv5bK3n0aSKMIyKKhKbPaGsuOKDix65G26F5n8D1rVcuOiCAc7KQmYNlTmwOmMURBbrZTXNkKSZwiRqvZ-rjXUHSkIfnDAL0eVOr3e8tT84RgQTVBZR4c2s4Oz1CD7wTvvpBkQPdpx-nKDYE3k-FXv1D3r_8WaqFfEEum9sLCwnUX5a5IjltMhopNb3UPFRENsnNmKjY3yR8HaREJkAP0MrRu_55uuX_2e335fs6wN2B8KEnbdmnNrSL8FsD07N7R00dy5jxKc5unWDT3PE5zmKaS8Ob-gu6XZw6B-ZKxrU</recordid><startdate>20230525</startdate><enddate>20230525</enddate><creator>Madhavan, Mathangi</creator><creator>Jaiswal, Devina</creator><creator>Karlberg, Sarah</creator><creator>Duggan, Alexis</creator><creator>Almarshad, Hassan A</creator><creator>Claffey, Kevin P</creator><creator>Hoshino, Kazunori</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7080-7825</orcidid></search><sort><creationdate>20230525</creationdate><title>Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids-Older spheroids reduce interstitial space and become stiffer</title><author>Madhavan, Mathangi ; Jaiswal, Devina ; Karlberg, Sarah ; Duggan, Alexis ; Almarshad, Hassan A ; Claffey, Kevin P ; Hoshino, Kazunori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c693t-3e81e1370ac4b2a259cbb613642d7d27249a1dd6aa63359b8b715685f716db9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Catabolites</topic><topic>Cell culture</topic><topic>Cells</topic><topic>Diameters</topic><topic>Drug delivery systems</topic><topic>Drugs</topic><topic>Electron microscopy</topic><topic>Evaluation</topic><topic>Growth models</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Image resolution</topic><topic>Mechanical properties</topic><topic>Medical equipment and supplies industry</topic><topic>Medical imaging</topic><topic>Medical test kit industry</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Methylene blue</topic><topic>Microenvironments</topic><topic>Microscopy</topic><topic>Microscopy, Electron</topic><topic>Modulus of elasticity</topic><topic>Multicellular tumor spheroids</topic><topic>Neoplasms</topic><topic>Nutrients</topic><topic>Oxygen</topic><topic>Patient outcomes</topic><topic>Physical Sciences</topic><topic>Physiology</topic><topic>Radiation</topic><topic>Research and Analysis Methods</topic><topic>Spheroids</topic><topic>Spheroids, Cellular</topic><topic>Stiffness</topic><topic>Transmission electron microscopy</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Madhavan, Mathangi</creatorcontrib><creatorcontrib>Jaiswal, Devina</creatorcontrib><creatorcontrib>Karlberg, Sarah</creatorcontrib><creatorcontrib>Duggan, Alexis</creatorcontrib><creatorcontrib>Almarshad, Hassan A</creatorcontrib><creatorcontrib>Claffey, Kevin P</creatorcontrib><creatorcontrib>Hoshino, Kazunori</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints database</collection><collection>Science (Gale in Context)</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>ProQuest Publicly Available Content database</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Madhavan, Mathangi</au><au>Jaiswal, Devina</au><au>Karlberg, Sarah</au><au>Duggan, Alexis</au><au>Almarshad, Hassan A</au><au>Claffey, Kevin P</au><au>Hoshino, Kazunori</au><au>Weihs, Daphne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids-Older spheroids reduce interstitial space and become stiffer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2023-05-25</date><risdate>2023</risdate><volume>18</volume><issue>5</issue><spage>e0286291</spage><epage>e0286291</epage><pages>e0286291-e0286291</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Multicellular cancer spheroids are an in vitro tissue model that mimics the three-dimensional microenvironment. As spheroids grow, they develop the gradients of oxygen, nutrients, and catabolites, affecting crucial tumor characteristics such as proliferation and treatment responses. The measurement of spheroid stiffness provides a quantitative measure to evaluate such structural changes over time. In this report, we measured the stiffness of size-matched day 5 and day 20 tumor spheroids using a custom-built microscale force sensor and conducted transmission electron microscopy (TEM) imaging to compare the internal structures. We found that older spheroids reduce interstitial spaces in the core region and became significantly stiffer. The measured elastic moduli were 260±100 and 680±150 Pa, for day 5 and day 20 spheroids, respectively. The day 20 spheroids showed an optically dark region in the center. Analyzing the high-resolution TEM images of spheroid middle sections across the diameter showed that the cells in the inner region of the day 20 spheroids are significantly larger and more closely packed than those in the outer regions. On the other hand, the day 5 spheroids did not show a significant difference between the inner and outer regions. The observed reduction of the interstitial space may be one factor that contributes to stiffer older spheroids.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37228139</pmid><doi>10.1371/journal.pone.0286291</doi><tpages>e0286291</tpages><orcidid>https://orcid.org/0000-0002-7080-7825</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2023-05, Vol.18 (5), p.e0286291-e0286291
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_2819261079
source PubMed Central; ProQuest Publicly Available Content database
subjects Biology and Life Sciences
Breast cancer
Cancer therapies
Care and treatment
Catabolites
Cell culture
Cells
Diameters
Drug delivery systems
Drugs
Electron microscopy
Evaluation
Growth models
Humans
Hypoxia
Image resolution
Mechanical properties
Medical equipment and supplies industry
Medical imaging
Medical test kit industry
Medicine and Health Sciences
Metabolism
Methylene blue
Microenvironments
Microscopy
Microscopy, Electron
Modulus of elasticity
Multicellular tumor spheroids
Neoplasms
Nutrients
Oxygen
Patient outcomes
Physical Sciences
Physiology
Radiation
Research and Analysis Methods
Spheroids
Spheroids, Cellular
Stiffness
Transmission electron microscopy
Tumor Microenvironment
Tumors
title Electron microscopy imaging and mechanical characterization of T47D multicellular tumor spheroids-Older spheroids reduce interstitial space and become stiffer
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T12%3A05%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Electron%20microscopy%20imaging%20and%20mechanical%20characterization%20of%20T47D%20multicellular%20tumor%20spheroids-Older%20spheroids%20reduce%20interstitial%20space%20and%20become%20stiffer&rft.jtitle=PloS%20one&rft.au=Madhavan,%20Mathangi&rft.date=2023-05-25&rft.volume=18&rft.issue=5&rft.spage=e0286291&rft.epage=e0286291&rft.pages=e0286291-e0286291&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0286291&rft_dat=%3Cgale_plos_%3EA750653743%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c693t-3e81e1370ac4b2a259cbb613642d7d27249a1dd6aa63359b8b715685f716db9f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2819261079&rft_id=info:pmid/37228139&rft_galeid=A750653743&rfr_iscdi=true